ADO-Studientreffen Melanom Adjuvant/Neoadjuvant · abdomen and pelvis. ... • Unstable hyperthyroidism or hypothyroidism • Diagnosis of immunodeficiency ... End of study: LPLV

ZDO

ADO-StudientreffenMelanom – Adjuvant/Neoadjuvant

Thomas EigentlerDresden, 22.09.2016

ZDO

Stadium II

ZDO

EORTC-18081Adjuvant Pegylated-Interferon-alpha2b (SylatronTM) for 2 Years Versus

Observation in Patients With an Ulcerated Primary Cutaneous Melanoma WithT(2-4)bN0M0: a Randomized Phase III Trial of the EORTC Melanoma Group

• Patienten mit ulzerierten Primärmelanomen habeneine ungünstigere Prognose (AJCC 2010)

• In Vorstudien haben Patienten mit ulzeriertenPrimärmelanomen in Subgruppenanalysen besondersvon einer ajduvanten Therapie profitiert

ZDO

EORTC-18991PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage

III (TxN1-2M0) Melanoma Patients: a Randomized Phase III Trial

* Nur Patienten mit Mikrometastasen im SN

ZDO

Firstline

Patients with an

ulcerated

melanoma with

Breslow >1 mm,

N0M0

• 1200 patients

• stages IB-IIC

tumor-free

R

A

N

D

O

M

I

Z

A

T

I

O

N

ARM A

Biological: PEG IFN

alfa-2b 3µg/kg weekly

injections for 2 y.

ARM B

No Intervention:

Observation

1:1

EORTC-18991PEG-Intron Observation After Regional Lymph Node Dissection in AJCC Stage

III (TxN1-2MO) Melanoma Patients: a Randomized Phase III Trial

ZDO

EORTC-18081Adjuvant Pegylated-Interferon-alpha2b (SylatronTM) for 2 Years Versus


Primary Outcome Measures: • Relapse-free survival (RFS)

[Time Frame: 6.3 years from first patient in]

Secondary Outcome Measures: • Occurrence of Adverse Events [Time Frame: 6.3 years from first patient in]

• Overall survival (OS) [Time Frame: 7.8 years from first patient in]

• Distant metastases-free survival (DMFS) [Time Frame: 7.8 years from first patient in]

• Quality of life [Time Frame: 6 years from first patient in]

ZDO

EORTC-18081Adjuvant Pegylated-Interferon-alpha2b (Sylatron TM) for 2 Years Versus


Inclusion Criteria:

• Subjects must be between 18-70 years old.

• Subjects must have histologically documented ulcerated primary cutaneous melanomas with T(2-4)b N0M0.

• Adequate resection of ulcerated primary cutaneous melanoma. 1 to 2 cm normal tissue excision margins according to Breslow thickness are recommended. …

• SNB must occur within 12 weeks prior randomization.

• Subjects must have an ECOG performance status of 0 or 1

• Subjects must have adequate bone marrow, renal and hepatic function as defined by the following parameters obtained up to maximum 12 weeks prior to randomization:

– WBC >= 3.0 x 109/L

– Neutrophils > 1.5 x 109/L

– Platelets > 100 x 109/L

– Hemoglobin >= 9 g/dL or 5.6 mmol/L

– Adequate Renal and Hepatic function:

– Serum creatinine < 2.0 mg/dL or < 140 µmol/L

– SGOT and SGPT < 2 times upper normal limit of laboratory normal (ULN)

ZDO



Exclusion Criteria:

• No mucosal melanoma nor ocular melanoma.

• No evidence of nodal involvement confirmed by sentinel lymph node biopsy (SNB). Sentinel Node staging after the excision of the primary must be done between the date of final excision of the primary and the date of randomization.

• No evidence of regional nor distant lymph node metastases nor satellites/in-transit metastases (even if they have been resected).

• No evidence of distant metastasis on clinical examination, CT/MRI of full chest, abdomen and pelvis. Neck CT/MRI if head and neck primary.

• No clinical evidence of brain metastasis.

• …

ZDO



• Essen

• Kiel

• Lübeck

• Köln

• Heidelberg

• Mainz

• Mannheim

• Würzburg

ZDO

Stadium III

ZDO

EORTC-18071Adjuvant Immunotherapy With Anti-CTLA-4 Monoclonal Antibody (Ipilimumab)

Versus Placebo After Complete Resection of High Risk Stage III Melanoma: A Randomized, Double-blind Phase 3 Trial of the EORTC Melanoma Group

The Lancet Oncology 2015 16, 522-530DOI: (10.1016/S1470-2045(15)70122-1)

ZDO

EORTC-18071Adjuvant Immunotherapy With Anti-CTLA-4 Monoclonal Antibody (Ipilimumab) Versus

Placebo After Complete Resection of High Risk Stage III Melanoma: A Randomized, Double-blind Phase 3 Trial of the EORTC Melanoma Group

ZDO

MK3475-054 / EORTC-1325Adjuvant Immunotherapy With Anti-PD-1 Monoclonal Antibody Pembrolizumab

(MK- 3475) Versus Placebo After Complete Resection of High-risk Stage III Melanoma: A Randomized, Double- Blind Phase 3 Trial of the EORTC

• 900 patients• stage IIIA(1mm+; max.

20%)-IIIC• No evidence of disease• no intransit-mets• tumor tissue required

(PDL-1 expression)• Node-dissection

performed according to guidelines

RANDOMIZATION

ARM APembrolizumab 200mg IV Q3

for 1 Year

ARM BPlacebo IV Q3 for 1 Year

Crossover possible after PD

1:1

Primary Objectives: Recurrence-free survival (also in the subgroup of patients with PD-L1-positive tumor expression)

ZDO



Major Inclusion criteria:• Completely resected Stage III melanoma• Tumor tissue available for evaluation of PD-L1 expression• ECOG performance status of 0 or 1• Adequate organ function• No prior therapy for melanoma except surgery for primary melanoma lesions (or previously

treated with interferon for thick primary melanomas without evidence of lymph node involvement are eligible)

Major Exclusion criteria:• Mucosal or ocular melanoma• History of pneumonitis requiring treatment with steroids, interstitial lung disease• History of hematologic or primary solid tumor malignancy, unless no evidence of that disease

for 5Y • Active autoimmune disease that has required systemic treatment in past 2 years• Active infection requiring therapy• Unstable hyperthyroidism or hypothyroidism• Diagnosis of immunodeficiency• Systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior

to the first dose of study medication• Known history of human immunodeficiency virus (HIV), active Hepatitis B or C

ZDO



ZDO

ZDO



Country Number of sites interested Expected enrollment per year

Australia 14 211

Austria 2 20

Belgium 3 28

Czech Republic 1 15

Denmark 3 80

Finland 1 20

France 18 200

Germany 13 121

Russia 3 70

ZDO



Dear Investigators,

This is a reminder that we plan to close screening tomorrow 27-Jul-2016 11:59 PM PDT . No additional patients will be allowed to screen in the study.IMPORTANT REMARKS:1) Patients who have signed consent on or before 27-Jul should be registered in ORTA as soon as possible.2) Patients can only be registered (STEP 1) if they have consented and if surgery has been performed.If you have a problem enrolling patients as per above remarks , please contact the medical monitor.

Kind regards,

EORTC, Merck and Covance study team

ZDO

Stadium IV

ZDO

Screening/Baseline/Pre-Examination (3 weeks before start of treatment)Incl. shipment of tumor tissue to the central lab in Essen for confirmation of PD-L1 status

Therapy

Follow-Up: every 3 months after last treatment (until end of study)

End of study: LPLV FU of LP for a maximum of 2 years

Randomization

Arm ANivolumab Monotherapy

Arm BNivolumab + Ipilimumab

Arm CDouble Placebo Control

End of treatment visit

Treatment week 1-12

From week 12 onwards (2-weekly infusion of Nivolumab/Placebo) – max. 1 year

every 6 weeks: TraFo samples every 12 weeks: staging, ECOG, physical examination …(see protocol for details)

IMMUNEDA Phase II Randomized, Double-Blind Trial of Immunotherapy With Nivolumab or

Nivolumab Plus Ipilimumab Versus Double-Placebo Control as a Post-Surgical/Post-Radiation Treatment for Stage IV Melanoma With No Evidence of Disease

ZDO

Study Arm

w1 w2 w3 w4 w5 w6 w7 w8 w9 w10 w11 w12

A

Nivo3mg/kg+Ipi-Placebo

Nivo3mg/kg

Nivo-Placebo+Ipi-Placebo

Nivo3mg/kg

Nivo3mg/kg+Ipi-Placebo

Nivo3mg/kg


Nivo3mg/kg

B

Nivo1mg/kg+Ipi3mg/kg

Nivo-Placebo


Nivo-Placebo


Nivo-Placebo


Nivo-Placebo

C


Nivo-Placebo


Nivo-Placebo


Nivo-Placebo


Nivo-Placebo

followed by maintenance therapy: Nivolumab/Nivolumab-Placebo 2 weekly for up to 1 year or progression

Cross-over OPTION for subjects in the Double-Placebo control cohort (arm C):Upon documented disease progression in the eCRF (confirmed via tumor assessment using radiologic imaging), subjects in Arm C

may receive Nivolumab 3mg/kg monotherapy every 2 weeks until subsequent progression or for up to 1 year, whichever occurs first.



ZDO

Primary Objective:Estimate the efficacy of Nivolumab alone or in combination with Ipilimumab therapy in stage IV patients with no evidence of disease i.e. the primary endpoint is progression-free survival (PFS).

Major Inclusion Criteria:• Stage IV melanoma arising from a primary cutaneous site or metastatic from an unknown

primary site with no evidence of disease (NED) after surgery or radiation therapy (conducted within 8 weeks before enrolment)

• Known BRAF status• Minimum life expectancy of five years excluding their melanoma diagnosis• ECOG performance status of 0 or 1• Tumor tissue from the resected site of disease must be provided for biomarker analyses. In

order to be randomized a subject must have a PD-L 1 expression classification (positive (≥ 5% tumor cells expressing PD-L1) or negative (< 5% tumor cells expressing PDL1)).

Major Exclusion Criteria:• History of primary uveal or mucosal melanoma• Prior therapy with CTLA4 or PD1 antibodies• Any immunosuppressive therapy given within the past 30 days prior to study drug

administration (excluding physiologic steroid hormone replacement)• Known to be positive for HIV or other chronic infections (HBV, HCV).



ZDO

Teilnehmende ZentrenMannheim

Hannover

BuxtehudeRegensburg

Heilbronn

BerlinMünster

GeraMünchen

DresdenLudwigshafenEssen

LübeckMainz

Erfurt

Tübingen

LeipzigHeidelbergKiel

MindenFrankfurt



ZDO

MO28848 / EADO-NEO-VCNeoadjuvant Treatment With the Combination of Vemurafenib and

Cobimetinib (GDC-0973) in Limited Metastasis of Malignant Melanoma (AJCC Stage IIIC/IV) and Integrated Biomarker Study: a Single Armed Phase II EADO

ZDO

Endpoints:• Primary Endpoint: Percent of patients who actually become resectable and are

resected• Secondary Endpoint: Progression-free survival, Overall survival(OS), Safety-

tolerability, Inclusion criteria: • Adult patients, ≥ 18 years of age• Metastatic melanoma, stage IIIC or IV (AJCC 2010)• ECOG 0-1• MAP-kinase pathway inhibitor treatment-naïve • Positive for BRAF V600 mutation, preferentially to be shown from metastatic tumor

tissueExclusion criteria: • Candidates for direct surgery: patients with single site easily resectable metastasis • Major surgical procedure or significant traumatic injury within 2 weeks prior to first

dose of study drug treatment• Active central nervous system metastases except metastases after complete

resection or stereotactic irradiation and stable status for at least 3 months



ZDO

Teilnehmende Zentren

HannoverBuxtehudeEssenMainzTübingenKiel



ZDO

PH-L19IL2TNF-02/15Randomisierte, offene, kontrollierte, multizentrische Phase III Studie zur Bestimmung der Wirksamkeit der neoadjuvanten intratumoralenBehandlung mit L19IL2/L19TNF gefolgt von chirurgischer Entfernung

der Läsionen im Vergleich zu chirurgischer Entfernung alleine in Melanom-Patienten der klinischen Stufe III B/C

• Stadium IIIb/c• Operabel• Kumulativ mind. 1 cm

Tumordurchmesser• Alle Läsionen

injizierbar 21

4 P

atie

nte

n, 1

:1

Op innerhalb 4 Wochen

4 Injektionen, 1xWoche, Op 4 innerhalb 4 Wochen

Follo

w-U

p

ZDO

PH-L19IL2TNF-02/15

Endpoints:• Primary Endpoint: RFS rate after 1 year of randomization• Secondary Endpoint: Local RFS and DMFS after 1 year of randomization, RFS (2-/3-Y

RFS), OS• Safety• BiomarkersInclusion criteria: • Adult patients, ≥ 18 years of age• Metastatic melanoma, stage IIIB/C eligible for surgery (AJCC 2010)• At least one injectable cutaneous, subcutaneous, or nodal melanoma lesion (>=

10mm in longest diameter) or multiple injectable lesions that in aggregate have a longest diameter of >=10mm.

• ECOG 0-1Exclusion criteria: • Distant metastases• Uveal or mucosal melanoma

ZDO


HannoverEssenHeidelbergTübingenKiel

PH-L19IL2TNF-02/15Randomisierte, offene, kontrollierte, multizentrische Phase III Studie zur Bestimmung der Wirksamkeit der neoadjuvanten intratumoralen Behandlung mit L19IL2/L19TNF

gefolgt von chirurgischer Entfernung der Läsionen im Vergleich zu chirurgischer Entfernung alleine in Melanom-Patienten der klinischen Stufe III B/C

ZDO

PV10-MM-31PV-10 Intralesional Injection vs Systemic Chemotherapy or Oncolytic

Viral Therapy for Treatment of Locally Advanced Cutaneous Melanoma

• Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous melanoma metastases (AJCC Stage IIIB, IIIC or Stage IV M1a with no active nodal metastases)

• At least 1 cutaneous Target Lesion (each lesion > =10 mm in longest diameter or up to 5 lesions having a sum of longest diameters >= 10 mm).

22

5 P

atie

nte

n, 2

:1

DTIC (iv. 850 m/m2) or TMZ (po. 200 mg/m2 for 5 days), q28 or

Intralesional T-VEC on an initial 21 interval followed by consecutive 14 day intervals, until

CR, PD or study termination occurs.

Follo

w-U

p

PV-10 to all study lesions d1, q28 until CR, PD or study termination.

ZDO

Endpoints:• Primary Endpoint: Progression-free survival (PFS) • Secondary Endpoint: Complete response rate, Duration of complete response, OS• Safety and tolerabilityInclusion criteria: • Age 18 years or older, male or female• Recurrent, satellite or in-transit locally advanced cutaneous or subcutaneous

melanoma metastases• At least 1 cutaneous Target Lesion (each lesion > =10 mm in longest diameter or up

to 5 lesions having a sum of longest diameters >= 10 mm). Target Lesions should beat least 10 mm from any other lesion

• No lesion > 30 mm in longest diameter; and no more than 50 lesions• Performance Status: Eastern Cooperative Oncology Group (ECOG) 0-2Exclusion criteria: • Presence or history of visceral melanoma metastasis• Presence of active nodal metastases



ZDO


KielHannoverEssenQuedlinburgTübingenDresdenMainzBerlin



Haut-

Tumor-

Zentrum

Hannover

HTZHAbteilung und/oder Titel

Abteilung und/oder Titel

Datum

Melanom palliativ –

Immunonkologisch

Ralf GutzmerKlinik für Dermatologie, Allergologie und Venerologie

Haut-

Tumor-

Zentrum

Hannover

HTZH

HTZH

Gliederung

T-VEC

• T-VEC Monotherapie

• T-VEC plus Ipilimumab

• T-VEC plus Pembrolizumab

Keynote 252 (MSD/Merck)

BoneMet (IIT, Hannover/Essen)

HTZH

Was ist T-VEC?

Talimogene Laherparepvec

Modifiziertes Herpesvirus

HTZH

Effekte von T-VEC

Lawler&Chiocca, J Clin Oncol 2015

HTZH

T-VEC: Monotherapie-Studie (Study T-Vec 20120325)

Multicenter, Open-label, Single-arm Trial to Evaluate theCorrelation Between ORR and Baseline Intratumoral CD8+ Cell

Density in Subjects With Unresected Stage IIIB to IVM1c Melanoma Treated With T-Vec

Primärer Endpunkt: Korrelation zwischen ORR und intratumoraler CD8+ Zell-Dichte vor Therapie

HTZH


HTZH

Estimated Enrollment: 110Global Study Start Date:Recruitment closed

April 2015Q2/2016

Estimated Study Completion Date: November 2018Estimated Primary Completion Date: December 2017 (Final data collection

date for primary outcome measure)


HTZH

Weltweit 45 Studienzentren4 deutsche Studienzentren:• Essen• Frankfurt/Main• Hannover• Heidelberg

2 österreichische Studienzentren:• Salzburg• Wien

14 Patienten in Deutschland rekrutiert


HTZH

Ipilimumab ± T-Vec in unresected melanoma (Study T-Vec 20110264)

HTZH

Global Study Start Date: February 2013Estimated Study Completion Date: November 2017Estimated Primary Completion Date: May 2016 (Final data collection date

for primary outcome measure)


Erste Ergebnisse am 28.09.2016 auf dem ESMO Kongress erwartet

HTZH

Weltweit 40 Studienzentren

3 deutsche Studienzentren:• Göttingen• Kiel• Tübingen

10 Patienten in Deutschland rekrutiert


HTZH

Pembrolizumab +- T-VEC (Study T-Vec 20110265)

• A Phase 1b/3, Multicenter, Open-label Trial of Talimogene Laherparepvec in Combination With Pembrolizumab (MK-3475) for Treatment of Unresected,Stage IIIB to IVM1c Melanoma (MASTERKEY-265)

HTZH

(abgeschlossen, nicht in D)

Pembrolizumab +- T-VEC (Study T-Vec 20110265)

HTZH

MASTERKEY-265 Phase 3 Study Design

N = 660

1:1

N = 330

N = 330

Pembrolizumab 200mg IV Q3W

T-VEC Intralesional

Pembrolizumab 200mg IV Q3W

T-VEC placebo Intralesional

Primary Endpoints: PFS and OS

R

• Unresectable stage III or

IV melanoma

• Treatment naive

– Prior BRAFi allowed

• Injectable lesions

Long G V et SMR 2015

HTZH

62 Zentren weltweit

Studienzentren D

• Dresden

• Hannover

• Kiel

• Regensburg

• Tübingen

• Weitere in Planung

Masterkey 265

Studienzentren CH

• Geneve

• Lausanne

• Zürich

Studienzentren A

• Salzburg

HTZH

T-VEC

Ansprechpartner bei Amgen:

Dr. med. Markus Schill

Senior Medical Advisor Immuno-Oncology

AMGEN GmbH

Hanauer Str. 1, 80992 München

Tel.: +49 (0)89 – 149 096 1492

Fax: +49 (0)89 – 149 096 2492

[email protected]

mailto:[email protected]

HTZH

Keynote 252-Studie

A Phase 3 Study of Pembrolizumab + Epacadostat or Placebo in Subjects With Unresectable or Metastatic Melanoma

Anderer Name: ECHO-301 (Epacadostat Clinical Development in Hematology and Oncology)

HTZH

Keynote 252-Studie

Epacadostat: IDO1-Inhibitor

IDO1: Indoleamine 2,3 dioxygenase 1, metabolisiert Tryptophan

[Not approved] FOR MEDICAL INFORMATION PURPOSES ONLY. NOT FOR PROMOTIONAL USE. DO NOT COPY, DISTRIBUTE OR OTHERWISE REPRODUCE.

Best Overall Response by RECIST 1.1:

Melanoma

Efficacy Evaluable* Patients,

n (%)

Melanoma

(n=19)

25 mg BID

(n=2)

50 mg BID

(n=12)

100 mg BID

(n=4)

300 mg BID

(n=1)

ORR (CR+PR) 10 (53) 1 (50) 5 (42) 4 (100) 0

CR 3 1 2 0 0

PR 7 0 3 4 0

SD 4 1 2 0 1

DCR (CR+PR+SD) 14 (74) 2 (100) 7 (58) 4 (100) 1 (100)

PD 5 (26) 0 5 (42) 0 0

52

*By data cutoff for efficacy (October 1, 2015), patients had at least 1 postbaseline scan or discontinued or died before the first postbaseline scan.

• In patients who were treatment-naive for advanced/metastatic melanoma (n=16):

– ORR 56%

– DCR 75% Phase Ib-Studie: Hamid et al., SMR 2015

[Not approved] FOR MEDICAL INFORMATION PURPOSES ONLY. NOT FOR PROMOTIONAL USE. DO NOT COPY, DISTRIBUTE OR OTHERWISE REPRODUCE.

Best Overall Response by RECIST 1.1:

Melanoma

Efficacy Evaluable* Patients,

n (%)

Melanoma

(n=19)

25 mg BID

(n=2)

50 mg BID

(n=12)

100 mg BID

(n=4)

300 mg BID

(n=1)

ORR (CR+PR) 10 (53) 1 (50) 5 (42) 4 (100) 0

CR 3 1 2 0 0

PR 7 0 3 4 0

SD 4 1 2 0 1

DCR (CR+PR+SD) 14 (74) 2 (100) 7 (58) 4 (100) 1 (100)

PD 5 (26) 0 5 (42) 0 0

53

*By data cutoff for efficacy (October 1, 2015), patients had at least 1 postbaseline scan or discontinued or died before the first postbaseline scan.

• In patients who were treatment-naive for advanced/metastatic melanoma (n=16):

– ORR 56%

– DCR 75% Phase Ib-Studie: Hamid et al., SMR 2015

HTZH

Keynote 252 – Endpunkte

Primär

• Progression-free survival (RECIST 1.1)

• Overall survival

Sekundär

• Objective response rate (RECIST 1.1)

• Safety and tolerability

HTZH

Keynote 252 – Haupt-Einschlusskriterien

• Have histologically or cytologically confirmed melanoma

• Have unresectable Stage III or Stage IV melanoma

• A minimum of 1 measurable lesion by CT or MRI

• Provide a baseline tumor biopsy

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

HTZH

Keynote 252 – Haupt-Ausschlusskriterien

• Prior systemic treatment (except BRAF directed therapy)

• Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or IDO1 inhibitor or any other antibody or drug specifically targeting checkpoint pathways other than anti-CTLA-4 which is permitted in the adjuvant setting

HTZH

Keynote 252 – Logistik

• 600 Patienten

• 112 Zentren weltweit

• Zentren D

– Buxtehude

– Essen

– Hannover

– Kiel

– Tübingen

• Zentren CH

– Geneve

– Lausanne

– Zürich

HTZH

MSD Ansprechpartner

Infocenter

MSD 0800 / 673 673 673

[email protected]

HTZH

BoneMet Studie - Hintergrund

• ca. 25% der Melanompatienten haben Knochenmetastasen

• RankL-Antikörper Denosumab zugelassen bei Knochenmetastasen solider Tumore

• Immunologische Daten und klinische Kasuistiken legen synergistische Wirkung von Denosumab und Checkpoint-Inhibitoren nahe

HTZH

BoneMet - Design

• Evaluation of immunological effects of the RANKL-inhibitor Denosumab when administered concurrently with PD1-blocking antibodies (Nivolumab, Pembrolizumab) in patients with metastatic malignant melanoma with bone involvement

• Einarmige Studie

• IIT Hannover/Essen

HTZH

BoneMet - Endpunkte

• Primär

– Anzahl aktivierter T-Zellen im peripheren Blut

– Induktion von Interferon gamma im Plasma

• Sekundär

– Sicherheit

– Verträglichkeit

– Effektivität

HTZH

BoneMet - Logistik

• 20 Patienten

• 4 Zentren

• Sponsor: Hannover Clinical Trial Center

• LKP: Ralf Gutzmer, Hannover

• Translationale Untersuchungen: Jürgen Becker, Essen

• Beginn Rekrutierung: Q1/2017

Onkologisches Zentrum

Studientreffen ADO Dresden, 22.9.2016

Immunonkologische Studien, Melanom

PD Dr. med. Patrick Terheyden, MA

Stv. Klinikdirektor, Klinik für Dermatologie

Leiter des Hautkrebszentrums

05.1

0.2

016

POPULATION TREATMENT

Part 1 – Double-blind ** Part 2 – Open-label

ENDPOINTS

Phase IIIb/IV Checkmate 511A Randomized, Double-blinded Phase IIIb/IV Study of Nivolumab 3 mg/kg plus Ipilimumab 1 mg/kg vsNivolumab 1 mg/kg plus Ipilimumab 3 mg/kg in Treatment-naïve Subjects With Advanced Melanoma

Eligible patients

with unresect-

able stage III or

IV melanoma

(n=346)

• Treatment-naïve

• ECOG 0-1

Stratified by:

• PD-L1

expression*

• AJCC M stage

Nivolumab

3 mg/kg +

Ipilimumab

1 mg/kg Q3W

for 4 doses

Nivolumab

1 mg/kg +

Ipilimumab

3 mg/kg Q3W

for 4 doses

Treat until

progression***

OR unacceptable

toxicity****

Primary endpoint:

• Incidence of

drug-related

grade 3-5 AEs#

Secondary EPs:

• ORR#

• OS# & PFS#

Nivolumab

Flat Dose

480 mg Q4W(30 min infusion)

6 W

EE

KS

**6 W

EE

KS

**

R

1:1

* PD-L1 positive: ≥ 5% tumor cell surface staining. Validated PD-L1 assay is used for stratification of patients and efficacy analyses.

** 6 weeks treatment-free period from last dose in part 1 to part 2 monotherapy flat dose. Treatment in Part 1 will no be revealed until the end of the study.

*** Patients may be treated beyond initial RECIST v1.1-defined progression under protocol-defined circumstances and if considered by the investigator to

be experiencing clinical benefit and tolerating the study drug. Such subjects must discontinue therapy when further progression is documented.

**** Until disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.# Fixed timepoint: After 6 months from the first dose of study treatment.

www.clinicaltrials.gov (NCT02714218) – Status September 2016

AEs = Adverse Events, EP = Endpoint, ORR = Objective Response Rate, OS = Overall Survival, PFS =

Progression Free Survival

http://www.clinicaltrials.gov/

Brief Title: A Study of Two Different Dose Combinations of Nivolumab in Combination With Ipilimumab

in Subjects With Previously Untreated, Unresectable or Metastatic Melanoma

Brief Summary: The purpose of this study is to evaluate two different dose combinations of nivolumab

and ipilimumab in the treatment of melanoma.

Key Inclusion Criteria1:

Subject must have been diagnosed with stage III or/and stage IV histologically confirmed melanoma [per American

Joint Committee on Cancer (AJCC) staging system] that is unresectable or metastatic

Eastern Cooperative Oncology Group (ECOG) performance status of 0-1

Subject has not been treated by systemic anticancer therapy for unresectable or metastatic melanoma

Key Exclusion Criteria1:

Subjects with active brain metastases or leptomeningeal metastases

Subjects with ocular melanoma

Subjects with active, known or suspected autoimmune disease

Participants Germany: Essen, Heidelberg, Tübingen & München – Global: 57 Sites

Recruitment & Timelines:

Estimated Enrollment: 346 – Randomized to date in Germany: approx. 20 patients

Estimated Primary Completion Date: May 2017 (final data collection date for primary outcome measure)

Estimated Completion Date: April 2022

Phase IIIb/IV Checkmate 511A Randomized, Double-blinded Phase IIIb/IV Study of Nivolumab 3 mg/kg plus Ipilimumab 1 mg/kg vsNivolumab 1 mg/kg plus Ipilimumab 3 mg/kg in Treatment-naïve Subjects With Advanced Melanoma

www.clinicaltrials.gov (NCT02714218) – Status September 20161 For more information please visit www.BMSStudyConnect.com


POPULATION ENDPOINTSTREATMENT


AEs = Adverse Events, EP = Endpoint, mTTO = Median Time to Onset, mTTR = Median Time to Resolution,

ORR = Objective Response Rate, OS = Overall Survival, PFS = Progression Free Survival

* Patients may be treated beyond initial RECIST v1.1-defined progression under protocol-defined circumstances and if considered by the investigator to be

experiencing clinical benefit and tolerating the study drug. Such subjects must discontinue therapy when further progression is documented.

** Until disease progression, discontinuation due to toxicity, withdrawal of consent or the study ends.# Including AE management and outcomes of AEs when managed according to the BMS management algorithms.

Eligible patients

with unresectable

stage III or IV

melanoma (n=615)

• Treatment-naïve

• ECOG 0-2

• Mucosal & ocular

melanomas allowed

• No current disease

spread to the brain

Nivolumab 1 mg/kg +

Ipilimumab 3 mg/kg

Q3W for 4 doses

THEN Nivolumab

3 mg/kg Q2W

Treat until disease

progression*

OR unacceptable

toxicity**

Primary endpoint:

• Rate & frequency of

grade 3-5 treatment-

related, select AEs

Secondary EPs:

• Incidence, mTTO &

mTTR of all grade

3-4 select AEs#

• ORR, PFS & OS

Phase IIIb/IV Checkmate 401A Clinical Trial of Nivolumab Combined with Ipilimumab Followed by Nivolumab Alone as First Line Treatment of Patients With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma


68

Phase IIIb/IV CA209-401A Clinical Trial of Nivolumab Combined with Ipilimumab Followed by Nivolumab Alone as First Line Treatment of Patients With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma

Brief Title: Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line

Treatment for Patients With Advanced Melanoma

Brief Summary: The purpose of this study is to determine the effects of combination treatment of

Nivolumab with Ipilimumab in patients with previously untreated advanced Melanoma.


Potential subjects must have advanced Melanoma (stage III or IV as confirmed by biopsy) with spread to other sites

in the body and unable to be removed by surgery

Potential subjects must be newly diagnosed with advanced Melanoma and received no treatment for the

advanced disease. The subjects who received previous primary treatment and any additional treatment (which is given

after the primary treatment) are permitted if it was completed at least 6 weeks prior to study entry and if the side effects

of the treatment are resolved. If subjects received any of the following primary treatment previously; (they are not

permitted to be enrolled in the study: anti-CTLA-4, anti-PD-1, anti-PD-L1, anti-PD-L2, or any other drug specifically

targeting T-cell costimulation or checkpoint pathways such as anti-CD-137.

Potential subjects (with disease spread to brain) who previously received primary treatment are permitted if there

was no evidence of disease as confirmed by the MRI (at least 2 weeks after the primary treatment is complete and

with in 6 weeks of the first dose of the study drug). Potential subjects must not have received steroid treatment (>10

mg/day) for at least 2 weeks prior to study drug administration.



69

Phase IIIb/IV CA209-401A Clinical Trial of Nivolumab Combined with Ipilimumab Followed by Nivolumab Alone as First Line Treatment of Patients With Histologically Confirmed Stage III (Unresectable) or Stage IV Melanoma

Brief Title: Nivolumab Combined With Ipilimumab Followed by Nivolumab Monotherapy as First-Line

Treatment for Patients With Advanced Melanoma

Brief Summary: The purpose of this study is to determine the effects of combination treatment of

Nivolumab with Ipilimumab in patients with previously untreated advanced Melanoma.


There is no current (and not previously treated) disease spread to the brain

Subjects who received prior therapy with an anti-CTLA-4, anti-PD-1, anti PD-L1 or anti-PD-L2, anti-CD-137 agents

(or any other antibody or drug specifically targeting T-cell costimulation or checkpoint pathways) for adjuvant, neo-

adjuvant, or advanced melanoma treatment or as part of clinical trial

Subjects with autoimmune disease. Subjects with Type I diabetes mellitus, hypothyroidism only requiring hormone

replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not requiring systemic treatment, or conditions

not expected to recur in the absence of an external trigger are permitted to enroll

All side effects from previous primary treatments other than alopecia, fatigue, or peripheral neuropathy must have

resolved to Grade 1 or baseline before administration of study drug

Participants Germany: 17 Sites: Hannover, Erlangen, Erfurt, Ludwigshafen, Kiel,

Frankfurt, Berlin, Göttingen, Mainz, Dresden, Freiburg, Buxtehude, Schwerin, Leipzig, Lübeck,

Mannheim, Würzburg – Global: approx. 90 Sites


Estimated Enrollment: 615 – Treated to date in Germany: approx. 16 patients

Estimated Primary Completion Date: December 2021 (final data collection date for primary outcome measure)

Estimated Completion Date: December 2021



http://www.bmsstudyconnect.com/

70

Phase I/II CA186-107A Phase I/II Dose Escalation and Cohort Expansion Study of the Safety and Tolerability of Urelumab in

Combination With Nivolumab in Advanced/Metastatic Solid Tumors and B-cell Non-Hodgkins Lymphoma

Part 1 – Dose Escalation: Nivolumab plus Urelumab (CD137 / 4-1BB agonist)

Part 2 – Dose Expansion : Nivolumab Q2W plus Urelumab Q6W

Main tumor Types:

Melanoma (MEL), Non-small cell lung cancer (NSCLC), Squamous head and neck cancer (SCCHN),

Diffuse-large B-Cell Lymphoma (DLBCL)

Endpoints:

1° EP: Safety as measured by the rate of adverse events (AEs) and Serious Adverse Events (SAEs), is the

primary endpoint of this Phase 1/2 study. All subjects who receive at least one (full or partial) dose of Urelumab or

Nivolumab will be evaluated for safety during treatment and for up to 100 days in follow-up

Key 2° EPs: Best Overall Response (BOR), Objective response rate (ORR), Duration of Response (DOR),

Progression-free survival (PFS) rate



71



Brief Title: Study of the Safety and Tolerability of Urelumab Administered in Combination With

Nivolumab in Solid Tumors and B-cell Non-Hodgkins Lymphoma

Brief Summary: The purpose of this study is to determine which doses of Urelumab and Nivolumab are

safe and tolerable when they are given together.


For Dose Escalation: Subjects with any previously treated advanced (metastatic or refractory) solid tumor type and B-

cell non-Hodgkin lymphoma

For Cohort Expansion: Subjects must have a previously treated advanced solid tumor or B cell non-Hodgkin's

lymphoma to be eligible, ECOG performance status of 0 or 1

For certain subjects, willing and able to provide pre-treatment and on-treatment fresh tumor biopsy

Women of child-bearing potential and men must use an acceptable method of contraception during treatment and for

23 weeks after treatment for women and 31 weeks for men


Known central nervous system metastases or central nervous system as the only source of disease

Other concomitant malignancies (with some exceptions per protocol)

Active, known or suspected autoimmune disease

Uncontrolled or significant cardiovascular disease

History of hepatitis (B or C) or history of active or latent tuberculosis





Brief Title: Study of the Safety and Tolerability of Urelumab Administered in Combination With

Nivolumab in Solid Tumors and B-cell Non-Hodgkins Lymphoma

Brief Summary: The purpose of this study is to determine which doses of Urelumab and Nivolumab are

safe and tolerable when they are given together.

Participants Germany: Essen – Global: 12 sites


Estimated Enrollment: 240 – Randomized to date in Germany: approx. 12 patients

Estimated Primary Completion Date: December 2018 (final data collection date for primary outcome measure)

Estimated Completion Date: September 2019



University Hospital of Regensburg

A prospective phase I and consecutive phase II, two-arm,

randomized multi-center trial of temsirolimus in combination

with pioglitazone, etoricoxib and metronomic low-dose

trofosfamide versus dacarbazine (DTIC) in patients with

advanced melanoma

(Mel001 Study)

Communicative reprogramming of metastatic melanoma

in >= second-line therapy

Albrecht Reichle, Sebastian Haferkamp

Universität Regensburg

Medizinische Klinik III, Dermatologie

Regensburg, September 2016

Rationale

• Up-regulating tumor suppressor genes (e.g. PTEN) for

modulating tumor behavior

• ‚Normalizing‘ homeostatic pathways, e.g. Wnt/β-catenin

signaling

• Controlling melanoma-associated inflammation

• Targeting the late-stage overexpression of a nuclear

transcription factor (PPARgamma)

• Epigenetic modelling with metronomic low-dose chemotherapy

and transcriptional modulator

• Targeting the mitogen-activated protein kinase and

phosphoinositide 3-kinase/AKT/mTOR pathways, which are

activated in most cutaneous and uveal melanomas

Metastatic melanoma (>= second-line):

A randomized phase II trial

Combined modularized therapy versus DTIC (Mel001)

Temsirolimus 25 mg weekly

Pioglitazone 60 mg p.o. daily (PPAR alpha/gamma agonist)

Etoricoxib 60 mg p.o. daily (COX-2 inhibitor, PPAR beta antagonist)

Trofosfamide 50 mg thrice daily

The alterations in major components of the MAPK, such as BRAF and NRAS mutations, and mTOR pathways,

PTEN loss and AKT overexpression, seem to have substantial influence in melanoma progression

Treatment until progression or intolerable toxicity

Primary objective

Phase I: To determine the dose of temsirolimus to be used in phase

II part of the study: 25 mg weekly

Phase II (on-going): To determine objective response rate (ORR)

Secondary objectives To evaluate overall survival (OS)

To evaluate time to progression (TTP)

To evaluate time to partial response (time to PR or better)

(TPR)

To evaluate quality of life

To evaluate tolerability and safety

Key Inclusion Criteria

• Must be histologically diagnosed with metastatic melanoma or metastatic uveal melanoma and

LDH level > 0.8 ULN

• Subjects may receive study medication as >= second-line therapy following immune therapy

or failure of BRAF- and/or MEK targeting therapy independently of the BRAF mutation status

• Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2

• Documented brain metastases not allowed, unless the patient has completed successful local

therapy for central nervous system metastases and has been off of corticosteroids for at least 4

weeks before enrollment.

Planned Study Timelines:

Recruitment of patients is scheduled to

December 2017

The minimum follow-up time from last patient

recruited is 12 months


Participating centers of the current randomized phase II trial:

Further centers are wellcome!!

Dermatology Magdeburg

Dermatology, Homburg/Saar

Dermatology, Nuremberg

Dermatology, Mainz

Dermatology, Rechts d. Isar

Dermatology, Regensburg

Hämatology/Oncology Regensburg

22 Patienten ausstehend

Investigator-initiated trialSponsor: Universitätsklinikum Regensburg

Finanzielle Unterstützung durch Pfizer

Ansprechpartner:

Prof. Dr. Albrecht Reichle:

[email protected]

Tel.: +49-941-9445540

PD Dr. Sebastian Haferkamp

[email protected]

Tel.: +49-941-9449605

Studienzentrale: Frau Montag

Tel.: +49-941-9445536



Onkologisches Zentrum

Studientreffen ADO Dresden, 22.9.2016

Immunonkologische Studien, Melanom

Diskussion

05.1

0.2

016

NRAS+; BRAF Wildtyp

Katharina C. Kähler

Phase II Trial of Pimasertib Versus Dacarbazine in N-

Ras Mutated Cutaneous Melanoma

• Eine multizentrische, unverblindete, randomisierte Prüfung der

Phase II zu dem MEK-Hemmer Pimasertib oder Dacarbazin bei

zuvor unbehandeltem Patienten mit lokal fortgeschrittenen

oder metastastisch malignem, kutanem Melanom mit NRAS-

Mutation

• Sponsor: Merck Serono

•Augsburg

•Berlin

•Bonn

•Buxtehude

•Düsseldorf

•Erlangen

•Essen

•Frankfurt am Main

•Hamburg

•Hannover

•Kiel

•Köln

•Leipzig

•Magdeburg

•Mainz

•München

•Münster

•Plauen

•Tübingen

•Würzburg

The primary objective to demonstrate a significant improvement of PFS in Pim treatment

arm (investigator assessment) as compared to DTIC treatment arm was achieved (HR (95% CI): 0.59

(0.42,0.83); p= 0.0022), median PFS 13 weeks in Pim vs 6.9 weeks in DTIC treatment arm. A consistent

trend was observed in favor of Pim treatment arm across imaging end points (PFS, ORR,DCR; per

investigator and central read) and also considering prognostic factors. No substantial difference was

noted in OS. The results of the OS analysis were confounded due to study design (cross-over allowed,

41/64 DTIC patients crossed over to Pim treatment).The safety profile of Pimasertib was consistent

with previous studies and no new safety signals were identified.

Daten werden beim diesjährigen ESMO Kongress präsentiert

Ansprechpartner:Array

Zentren in Deutschland

• Essen

• Buxtehude

• Gera

• Heidelberg

• Homburg

• Ludwigshafen

• Lübeck

• München

• Hornheide

NIPAWILMA

Studienstart: Jan 2015 (1. Zentrum geöffnet)

FPI: 17.03.2015

Phase I abgeschlossen

ermitteltes Dosislevel Nintedanib: 200mg BID

Doppel-blinde Phase II ab KW34 gestartet

Rekrutierungs-Übersicht Phase I:

Site

No.

Offene

Zentren

Offen

seit

Pat.

gescree

nt

Erster

Pat.

gescreent

Letzter

Pat.

gescreent

Patienten

randomisie

rt

Erster Pat.

randomisie

rt

Letzter Pat.

randomisie

rt

01 Essen07.01.201

510

21.01.201

5

26.02.201

66 17.03.2015 07.03.2016

02 München08.01.201

53

12.01.201

5

06.10.201

50 - -

03 Heidelberg24.02.201

56

19.03.201

5

15.04.201

61 26.04.2016 -

04 Buxtehude10.03.201

51

26.08.201

5- 0 - -

05Münster/Hornheid

e

16.04.201

51

03.09.201

5- 1 15.10.2015 -

06 Gera21.10.201

50 - - 0 - -

07 Homburg06.01.201

50 - - 0 - -

08 Ludwigshafen20.11.201

52

29.01.201

6

04.02.201

62 25.02.2016 25.02.2016

09 Lübeck15.01.201

61

28.01.201

6- 0 - -

10 UK Münster03.02.201

60 - - 0 - -

Sum: 24 10

Kontakt:

Dirk Schadendorf, Prof. Dr.

+49 201-723 ext 4342,

[email protected]

PACMEL

Studienstart: Okt 2014 (1. Zentrum geöffnet)

FPI: 03.12.2014

Rekrutierungsende: 31.03.2016

Last Patient Last Visit: voraussichtlich 12/2016

Site No.

offene Zentren

Offen seit

Pat.

gescreent

letzter

Pat.gescreent

letzter

Pat.

gescreent

Pat.

randomisiert

erster Pat.

randomisiert

letzter Pat.

randomisie

rt

01 Essen17.10.201

417

10.11.201

4

18.03.201

613 05.12.2014 07.04.2016

02 Tübingen12.11.201

44

28.07.201

5

12.01.201

63 25.08.2015 15.01.2016

03 Köln19.11.201

45

16.12.201

4

29.07.201

53 02.02.2015 10.08.2015

04 Erfurt08.01.201

54

16.03.201

5

18.09.201

51 14.04.2015 -

05 Kiel03.02.201

50 - - 0 - -

06 Minden18.02.201

53

15.07.201

5

28.01.201

62 20.07.2015 09.02.2016

07Regensbur

g

19.03.201

50 - - 0 - -

08 Berlin23.03.201

107.04.201

- 1 11.05.2015 -

Kontakt:

• Dirk Schadendorf, Prof. Dr.

• +49 201-723 ext 4342

• [email protected]

Targeted BRAF-Phase I/II-

Studien

Lisa Zimmer

Folie 112TitelTargeted BRAF-Phase II+III22.9.2016 | L.Zimmer

Targeted BRAF-Phase I/II-Studien

•BOTTOM (IIT) Phase 2

•LOGIC II CLGX818X2109 Phase 2

•ImmunoCobiVEM (IIT) Phase 2

•IMMU-TARGET (IIT) Phase 1/2


BOTTOM

Biopsy- and Biology-driven optimization of targeted

therapy of metastatic melanoma (BOTTOM) in BRAF

Inhibitor non-pretreated and pretreated subjects with

advanced, non-resectable (Stage IIIC) or metastatic

(stage IV) BRAFV600E/K mutation-positive melanoma

Sponsor:

Universitätsklinikum Essen, Prof. Dr. Dirk Schadendorf


BOTTOM

• Primärer Endpunkt: Korrelation des klinischen Ansprechens in Woche 8 mit

molekularpathologischen Ergebnissen der Biopsien

• Sekundäre Endpunkte: ORR, DCR, PFS nach 6 Monaten, 1-Jahres OS, Safety

Kohorte A Kohorte B Kohorte C


Haupteinschlusskriterien:

• BRAF V600E/K mutiertes kutanes Melanom St IIIC/IV, nicht resezierbar

• ECOG 0/1

• Vorliegen einer biopsierbaren Läsion (darf keine RECIST-Läsion sein)

• Keine ZNS-Metastasen, außer:

– vorbehandelt (Stereotaxie, Chirurgie) und stabil ≥ 90 Tage, asymptomatisch,

nicht steroidpflichtig, keine Antikonvulsiva, Zustimmung durch Sponsor

erforderlich.

Hauptausschlusskriterien:

• Okuläres Melanom oder Schleimhautmelanom

• Schwere kardiovaskuläre Vorerkrankungen

• Retinalvenenverschluß, zentrale seröse Retinopathie

BOTTOM


Timelines:

BOTTOM

Rekrutierungsdauer: 15 Monate

Einschluss erster Patient: Q4 2015

Einschluss letzter Patient: Q2 2017

Studienende: Q2 2018 (= 1 Jahr nach 1. Therapiegabe

des letzten Patienten)


Aktuelle Zahlen:

BOTTOM- Rekrutierung

• LKP: Dirk Schadendorf

• Studienstart: Jul 2015 (1. Zentrum geöffnet)

• FPI: 30.11.2015

• Stand 8.9.2016, 7 Zentren in Deutschland geöffnet


Ansprechpartner UK Essen:

Julia Grimm

Mail: [email protected]

Phone: +49201-7232325

Ansprechpartner Alcedis:

Dr. Joachim Stump

Winchesterstr. 3

D- 35394 Gießen


Phone: +49 (0) 641/ 94436-0

BOTTOM


BOTTOM - Studientreffen


LOGIC II CLGX818X2109

A phase II, multi-center, open-label study of

sequential LGX818/MEK162 combination followed by a

rational combination with targeted agents after

progression, to overcome resistance in adult patients with

locally advanced or metastatic BRAFV600 melanoma

Sponsor: Array


• Primärer Endpunkt: ORR der Triple-Therapie nach Progress unter BRAFi/MEKi

• Sekundäre Endpunkte: Safety, Tolerability, PFS, DOR, TTR, DCR; nur

Part II: OS, ORR; genomische Alterationen des

Tumorgewebes, PK




• BRAF V600 mutiertes Melanom St IIIC/IV, nicht resezierbar

• ECOG ≤2

• Tumorgewebe verfügbar


• Symptomatische ZNS-Metastasen, außer:

– asymptomatisch und stabil ≥ 4 Wochen, nicht steroidpflichtig oder stabile

Steroiddosis über 4 Wochen.





Timelines:

• Einschluss erster Patient: Juli 2014

• Einschluss letzter Patient: 9. November 2015

• Voraussichtliches Studienende: 6. Januar 2017



Aktuelle Zahlen:

• Weltweite Rekrutierung, insgesamt 19 Zentren, davon 4 in Deutschland

Würzburg (Anja Gesierich), Köln (Cornelia Mauch), Heidelberg (Jessica

Hassel), München (Carlola Berking)

• Rekrutierung weltweit abgeschlossen: 157 Patienten

• Eingeschlossene Patienten in Deutschland: 37 Patienten



Aktuelle Zahlen:



Ansprechpartner:

ARRAY und PPD



Phase II, multicenter, open-label, randomized-controlled Trial

Evaluating the Efficacy and Safety of a Sequencing Schedule of

Cobimetinib plus Vemurafenib followed by Immunotherapy with

an anti- PD-L1 antibody Atezolizumab for the treatment in

patients with unresectable or metastatic BRAF V600 mutant

melanoma

Sponsor: Universitätsklinikum Essen, Prof. Dr. Dirk Schadendorf

ImmunoCobiVem


ImmunoCobiVem

• Primärer Endpunkt: Zeit bis PFS2

• Sekundäre Endpunkte: Sicherheit, Toxizität, OS, 1-,2-Jahres OS, 1-,2-Jahres-

DCR, PFS1, PFS3

• Exploratorische Studienziele: Translationale Analyse Tumorgewebe/Blut;

eMARS (electronic Medication Adherence

Reminder System)


ImmunoCobiVem – eMARS-Konzept

Run-In Phase (3 Monate = 12 Wochen)

Papier-Med.-Diary (Hauptstudie) Alcedis eMARS

• Patient: führt Papier-Med.-Diary und bringt dieses zu Visiten mit

• Arzt: überprüft Med.-Diary bei Visite und pflegt dies ins eCRF ein

• Patient: führt online Med.-Diary

• eMARS: erinnert Patient bei Nichteinnahme per SMS

• Arzt: überprüft Med.-Diary im eCRF bei Visite

Dosis per Zyklus (4 Wochen): • Vemurafenib (d1-d28): 960mg (4x240mg Tabletten) morgens und

abends• Cobimetinib (d1-d21): 60mg (3x20mg Tabletten) morgens

Patient: kommt zur Visite in W3, W5, W7, W9 und Ende W12

Pharmakovigilanz:

Prüfen der Patienten-

Einträge nach

festgelegtem Schema

Randomisation Phase

Ende der Run-In Phase:• Patient: beantwortet Patienten-Fragebogen elektronisch

Patienten können optional eMARS während Einnahme von Cobimetinib und Vemurafenib in Randomisation Phase weiter nutzen

Auswertung der Medikationsadhärenz nach 18 Monaten Studienlaufzeit

Technischer Support:

Telefon-Hotline und FAQ

im eCRF

Per Tablet am Zentrum



• BRAF V600 mutiertes kutanes Melanom St IIIB/IIIC/IV, nicht resezierbar

• Keine Vortherapie erlaubt

• ECOG 0/1, Tumorgewebe verfügbar

• Keine Hirnmetastasen außer, wenn behandelt (stereotaktisch oder

chirurgisch) stabil ≥4 Wochen, asymptomatisch, nicht steroidpflichtig

• LVEF≥50%, QTc ≤ 450 ms


• Leptomeningeale Metastasen, Meningeosis carcinomatosa

• Immunsuppressive Therapie innerhalb von 7d vor Studienstart



ImmunoCobiVem


Timelines:

ImmunoCobiVem

Rekrutierungsdauer: 15 Monate

Initiierung der ersten Zentren: ab 26.9.2016

Einschluss erster Patient: QIII 2016

Einschluss letzter Patient: QIV 2017

Dauer das Follow-up: 24 Monate nach Randomisierung des letzten

Patienten

Studienende: QI 2020 (= ‘Last Patient Last Visit’ in der FU-

Phase)



• Europaweite Rekrutierung, insgesamt 30 Zentren, davon 20 in Deutschland

ImmunoCobiVem


ImmunoCobiVem- 10 Zentren im Ausland


ImmunoCobiVem


Julia Grimm:


Phone: +49201-7232325


Dr. Joachim Stump

Winchesterstr. 3

D- 35394 Gießen


Phone: +49 (0) 641/ 94436-0


ImmunoCobiVem - Studientreffen


IMMU-TARGET

A randomized Phase I/II open label, multicentre study of

encorafenib plus binimetinib and PD-1 antibody pembrolizumab

in patients with unresectable or metastatic BRAF V600 mutant

melanoma.

Sponsor: Universitätsklinikum Essen, Prof. Dr. Dirk Schadendorf


• Der Dosisfindung in Phase I liegt ein Dosisreduktions-Schema zugrunde:

• In jedem Schritt werden dafür 3 Patienten in die Studie eingeschlossen

• Dosis-limitierende Toxizitäten (DLT) werden nach 42 Tagen nach dem

Start der Therapie (erste Pembrolizumab Gabe) bestimmt

• Primäres Studienziel: Sicherheit und Verträglichkeit

IMMU-TARGET – Studienaufbau Phase 1


• Primärer Endpunkt: PFS, PFS-Rate nach 12,18, 24 Monaten

• Sekundärer Studienendpunkte: Sicherheit, ORR, Overall survival, OS-

Rate nach 1- und 2-Jahren

IMMU-TARGET – Studienaufbau Phase 2



• BRAF V600 E oder K mutiertes Melanom St IIIB,IIIC/IV, nicht resezierbar

• Keine Vortherapie

• ECOG 0/1

• Keine Hirnmetastasen außer, wenn behandelt, stabil ≥4 Wochen,

asymptomatisch, nicht steroidpflichtig oder durchgängig Prednisolon

<10mg erhalten


• Leptomeningeale Metastasen, Meningeosis carcinomatosa

• Uvea-Melanom



IMMU-TARGET


Timelines:

Studienstart (First Patient First Visit): Q4 2016

Rekrutierungszeitraum 24 Monate

Rekrutierungsende (Last Patient First Visit): Q4 2018

Studienende (Last Patient Last Visit): Q4 2020

Datenbankschluss Q4 2021

IMMU-TARGET


IMMU-TARGET


• 17 Zentren in Deutschland


IMMU-TARGET


Julia Grimm:


Phone: +49201-7232325


Dr. Joachim Stump

Winchesterstr. 3

D- 35394 Gießen


Phone: +49 (0) 641/ 94436-0

Hautklinik und PoliklinikRhein-Main

HautkrebsZENTRUM

CL

Impfstudien/Uveamelanom

Carmen Loquai

23.09.2016


HautkrebsZENTRUM

CL

Gliederung

Impfstudie

RP-0003-01/Lipo-MERIT Studie

Uveamelanomstudie

FOCUS-PHP-OCM-301 Studie


HautkrebsZENTRUM

CL

RB_0003-01: Lipo-MERIT

Clinical first-in-human study dose escalation study evaluatingthe safety and tolerability of intravenous administration of atetravalent RNA-lipoplex cancer vaccine targeting the tumor-associated antigens NY-ESO-1, tyrosinase, MAGE-A3, and TPTEin patients with advanced melanoma


HautkrebsZENTRUM

150TRON gGmbH

Ultrasound-

guided

intranodal

injection

Local DC targeting

Tumor

Lymph nodeThymus

Spleen

Peyer‘s patch

Bone marrow

Excellent preclinical safety profile

Strong therapeutic antitumor activity

mRNA and DCs meet directly at injection site

Systemic DC targeting

Intravenous

injection

mRNA Vakzine für optimiertes DC-Targeting in vivo

MERIT (NCT01684241)

IVAC MUTANOME (NCT02035956)

Liposomal RNA vaccine targeting to DC

Universally applicable for almost all types of tumor antigen

Induction of combined innate and adaptive immunity

Triggering of type I IFN network

Strong therapeutic antitumor activity

RNA

RNA(LIP)

Kranz, Diken et al, Nature 534, (June 2016)


HautkrebsZENTRUM

CL


Indikation: Malignes Melanom Stadium IIIB-IV

Phase I-Studie, multizentrisch, open-label, nicht-randomisiert

Teilnehmende Zentren: Mainz (LKP), Mannheim, Heidelberg,

Frankfurt

Anzahl der Patienten: 39-51 (5-6 Kohorten)


HautkrebsZENTRUM

CL


Erster Patienteneinschluß: 27.05.2015

Letzter Patienteneinschluß: voraussichtlich Q4 2017

Primäre Endpunkte: Sicherheit, Tolerabilität, Biologische Effekivität

Sekundäre Endpunkte: Anprechen messbarer Tumorläsionen

gemäß irRECIST 1.1

Stand Sept. 2016: 8 eingeschlossene Patienten, 4 Patienten unter

Behandlung


HautkrebsZENTRUM

CL

Gliederung

Impfstudie

RP-0003-01/Lipo-MERIT Studie

Uveamelanomstudie

FOCUS-PHP-OCM-301 Studie


HautkrebsZENTRUM

CL

PHP-OCM-301-Studie: FOCUS

A Randomized, Controlled, Phase 3 Study to Evaluate the

Efficacy, Safety and Pharmacokinetics of Melphalan/HDS

Treatment in Patients with Hepatic-Dominant Ocular

Melanoma


HautkrebsZENTRUM

CL

Studiendesign

Uveamelanom,

überwiegend

hepatisch

metastasiert

Melphalan/HDS* 3,0

mg/kgKG, bis zu 6x

Kontrolle: DTIC,

transarterielle

Chemoembolisation

(TACE), Ipilimumab,

Pembrolizumab

*Hepatic Delivery System

Randomisierung: 1:1


HautkrebsZENTRUM

CL

Hepatic Delivery System (Delcath Device System)


HautkrebsZENTRUM

CL

Studiendesign

Geplante Patientenzahl: 240

Anzahl der Zentren: 20

Zentren in Deutschland: 4 (Berlin, Marburg, Regensburg, Mainz)

Primärer Endpunkt: Gesamtüberleben

Sekundärer Endpunkt: Progressionsfreies Überleben, ORR

Geöffnet zur Rekrutierung!

CL

Melanom-Hirnmetastasen

Friedegund Meier, Dresden

ADO - Studientreffen

Dresden, 22.09.2016

A Phase II, Open-Label, Multicentre

Study of Dabrafenib plus Trametinib

in Subjects with BRAF Mutation-

Positive Melanoma that has

Metastasized to the Brain

BRF117277 / COMBI-MB

Sponsor: Novartis

Clinicaltrials.gov: NCT02039947

BRF117277/COMBI-MB: A Phase II, Open-Label, Multicentre

Study of Dabrafenib plus Trametinib in Subjects with BRAF

Mutation-Positive Melanoma that has Metastasized to the Brain

Cohort A (N=75)

V600E (centrally confirmed)

Asymptomatic, ECOG 0-1

Without prior local therapy

Cohort B* (N=15)

V600E (locally confirmed)


With prior local therapy

Cohort C* (up to N=15)

V600D/K/R (locally confirmed)


With or without prior local therapy

Cohort D* (N=15)

V600D/E/K/R (locally confirmed)

Symptomatic, ECOG 0-2

With or without prior local therapy

• Cutaneous melanoma

• ≤ 2 systemic therapies

• ≥1 measurable brain lesion

N = 120

Dabrafenib 150 mg BID +

Trametinib 2 mg QD

Primary endpoint: Intracranial response (IR)

Secondary endpoints: extracranial response (ER), overall response (OR), disease control (intracranial, extracranial, and

overall), PFS, OS, and duration of all response.


*Rekrutierung beendet für

Kohorten B-D

Ein- und Ausschlusskriterien

Main inclusion criteria:

•Stage IV cutaneous melanoma (metastatic to the brain), and determined to be BRAF V600E/K/D/R

mutation-positive

•Systemic naïve or received ≤ 2 previous systemic treatment regimens for metastatic

melanoma. Prior systemic treatment in the adjuvant setting is allowed. Ipilimumab treatment must

end at least 8 weeks prior to enrollment.

Main exclusion criteria:

-Subjects with ocular or mucosal melanoma

-Neurological symptoms related to brain metastasis except for Cohort D where subjects can be

symptomatic.

-Prior treatment with a BRAF inhibitor or a MEK inhibitor.

-Treatment with stereotactic radiosurgery within 14 days, or treatment with whole-brain radiation

within 28 days prior to study treatment.


Rekrutierung

Aktueller Status (25. Aug. 2016):

• Enrolement closed

• 6 patients enrolled in 7 sites in

Germany:

C. Berking, München

C. Garbe, Tübingen

R. Gutzmer, Hannover

J. Hassel, Heidelberg

A. Hauschild, Kiel

M. Kaatz, Gera

C. Mauch, Köln

* delayed participation of Germany due to BfS approval

Clinicaltrials.gov: NCT02039947; data on file.

Timelines:

• FPFV (global): 21. Feb 2014

• FPFV (Germany)*: 04. Dec 2014

• LPFV : 22 July 2016

• 1st results to be presented @

ASCO 2017 (planned)

Ansprechpartner des Sponsors

Kerstin Patzolt (project management)

[email protected]

Phone +49 6105-9430-246


Buparlisib in Melanoma Patients

Suffering From Brain Metastases

CBKM120ZDE01T / BUMPER

Sponsor: Universitätsklinikum Tübingen


An open-label, uncontrolled, single arm phase II trial of

buparlisib in patients with

metastatic melanoma with brain metastases

not eligible for surgery or radiosurgery

•BRAFwt failed prior

immune checkpoint inhibitor

•BRAFV600 failed BRAFi

•Not eligible for

surgery or radiosurgery

•Melanoma brain metastases

•Asymptomatic, symptomatic

•ECOG 0-2

N = 22

Buparlisib 100 mg daily

p.o.

Primary endpoint: Intracranial disease control rate (IC-DCR; CR + PR + SD) assessed by investigators (modified RECIST 1.1)

Secondary endpoints: ORR, duration of response, PFS, OS, safety


In Melanom-Hirnmetastasen

ist der PI3K-AKT-Signalweg hyperaktiviert(Davies et al, Clin Cancer Res 2009;

Meier et al, J Clin Oncol 30, 2012 (suppl; abstr 8526);

Niessner et al, Cancer Medicie 2013;

Chen G et al, Clin Cancer Res 2014)

Der PI3K-Inhibitor Buparlisib hemmt das

Wachstum von Melanomhirnmetastasen-

zellen in vitro und in vivo(Meier et al, J Clin Oncol 31, 2013 (suppl; abstr e20050);

Chen G et al, Clin Cancer Res 2014; Niessner et al, Clin

Cancer Res 2016) BRAFi

MEKi

PI3Ki

Melanom-Hirnmetastasen:

PI3K / AKT – Inhibitoren - Rationale

16 20 23 27 30

16 20 23 27 30

days p.o.

days p.o.

M13 B

up

arl

isib

M14 S

HA

MDer PI3K-Inhibitor Buparlisib hemmt

das Wachstum von Melanom-HirnmetastasenMRI

Niessner et al, Clin Cancer Res 2016


Main inclusion criteria

•Histologically confirmed diagnosis of melanoma

•Pats. must have shown evidence for PD in the brain by MRI without leptomeningeal

disease

•Pats. must not be eligible for surgery or radiosurgery

•Patients BRAF V600 wildtype: must have objective evidence of progressive disease

during or following treatment with an immune checkpoint inhibitor

•Patients BRAF V600 mutation positive: must have objective evidence of

progression of disease during or following treatment with a BRAF inhibitor

•Life expectancy > 8 weeks

•ECOG performance status < 2

•Time interval between last day of previous anti-tumour local or systemic treatment

and first dose of BKM120:

– 14 days elapsed from last treatment with surgery or radiosurgery

– 28 days elapsed from last treatment with whole brain radiation

– 28 days have elapsed from last dose of approved or investigational chemo-,

cytokine-, immune-, biological-, or vaccine-therapy



Main exclusion criteria

•Leptomeningeal disease

•Requirement of >4 mg dexamethasone daily

•Participants with the following mood disorders as judged by the Investigator or a

psychiatrist, or as result of participant’s mood assessment questionnaire:

– history of or active major depressive episode

– bipolar disorder

– obsessive-compulsive disorder

– Schizophrenia

– suicidal attempt or ideation

– homicidal ideation

– ≥ CTCAE grade 3 anxiety


Rekrutierung

Aktueller Status (13. Sept. 2016)

• 9 patients enrolled

• 2 active sites in Germany

Thomas Eigentler, Tübingen

Claus Garbe, Tübingen

Friedegund Meier, Dresden


Timelines:

• Study Start Date:

– July 2015 (planned)

– October 2015

• Estimated Study Completion

Date: July 2018

• Estimated Primary Completion

Date: December 2017

(Final data collection date for

primary outcome measure)

Ansprechpartner

PD Dr. Thomas Eigentler

[email protected]

Phone +49 7071 298 5748

Prof. Dr. Friedegund Meier

[email protected]

Phone +49 351 458 19505


An open label phase II study to evaluate

safety and efficacy of combined treatment

with ipilimumab and nivolumab

in patients with four and more

symptomatic brain metastases of melanoma

CA209-429 / BRAINIP trial

Sponsor: Universitätsklinikum Tübingen

BRAINIP

An open label phase II study to evaluate

safety and efficacy of combined treatment

with ipilimumab and nivolumab

in patients with four and more

symptomatic brain metastases of melanoma

•Without and with previous therapy

•Not eligible for surgery or

radiosurgery

• > 4 symptomatic melanoma

brain metastases

•ECOG 0-2

•Life expectancy >3 months

N = 68

NIVO 1mg/kg + IPI 3mg/kg

Q3W for 4 doses

then NIVO 3mg/kg Q2W

Primary endpoint: Intracranial disease control rate (IC-DCR; CR + PR + SD) at 6 months of treatment assessed by investigators

(RECIST 1.1 and iRANO)

Secondary endpoints:

mOS, mPFS

Percentage of pats in whom stereotactic irradiation or surgery of all metastases becomes applicable after PR

Tolerability

BORR at 6 months of treatment (RECIST 1.1)

Cognitive function

QoL

BRAINIP


Main inclusion criteria

•Presence of four or more active brain metastasis

confirmed/evaluated by MRI

•Subjects with active brain metastases will be defined as subjects

with brain metastases and any of the following focal neurological

deficits, seizures, headache or any other neurological and/or

psychiatric alteration that can be timely related to the diagnosis of

CNS disease

•Subjects naïve for systemic treatment are eligible

•Subjects pre-treated with systemic immunotherapy, targeted therapy

or chemotherapy, are eligible.

•Subjects with prior local therapy of brain metastases are eligible

•ECOG Performance Status 0, 1or 2

•Expected life expectancy of more than three months

BRAINIP

Main exclusion criteria

• Ocular melanoma diagnosis

• Subjects, whose melanoma brain metastases were previously treated with

systemic therapy with the combination of CTLA-4 and PD-1 antibodies, are

not eligible.

• Active infection requiring systemic therapy

• Active, known or suspected autoimmune disease. Subjects with controlled

Type I diabetes mellitus, hypothyroidism only requiring hormone

replacement, skin disorders (such as vitiligo, psoriasis, or alopecia) not

requiring systemic treatment, or conditions not expected to recur in the

absence of an external trigger, are permitted to enroll.

• Interstitial lung disease that is symptomatic or may interfere with the

detection or management of suspected drug-related pulmonary toxicity.

• Patients should be excluded if they have positive test for hepatitis B virus

surface antigen (HBs Ag) or hepatitis C virus ribonucleic acid (HCV

antibody) indicating acute or chronic infection.

• Patients should be excluded if they have known history of testing positive

for human immunodeficiency virus (HIV) or known acquired

immunodeficiency syndrome (AIDS).

Ein- und Ausschlusskriterien BRAINIP

Rekrutierung

Aktueller Status (13. Sept. 2016)

• 0 patients enrolled

• 15 sites in Germany (planned)


Timelines:

• Study Start Date (FPFV)

Date: October 2016 (planned)

• LPLV

Date: September 2018

• End of Study

Date: September 2019

BRAINIP

Ansprechpartner

PD. Dr. Thomas Eigentler

[email protected]

Phone +49 7071 298 5748

Prof. Dr. Claus Garbe

[email protected]

Phone +49 7071 298 7110


BRAINIP

Radiomics to identify MRI parameters

that might be predictive of good response or side effects179

Radioonkoloogie

E. Troost

Dermatoonkologie

F. Meier

Neuroradiologie

J. Linn

Dresden

Tübingen

Heidelberg

ML30010 RadioCoBrim

FPI Q1 2017 (planned)

1. Shi H et al. Cancer Discov. 2014;4:69-79. 2. Trunzer K et al. J Clin Oncol. 2013;31:1767-1774. 3. Paraiso K et al. Br J Cancer. 2010;102:1724-1730. 4. Long GV et al. J Clin Oncol. 2014;32(5S):9011. 5. Ribas A et al. Lancet Oncol. 2014;15:954-965. 6. Su F et al. New Engl J Med 2012;366:207-215.

Rationale

Most common mechanism of acquired resistance to

vemurafenib is MAPK reactivation through MEK1,2

MEK + BRAF inhibition prevents the development of acquired resistance in preclinical models3

MEK + BRAF inhibition (dabrafenib + trametinib4 phase

3 and vemurafenib + cobimetinib phase 1/2)5 improved

response rates and PFS in BRAF inhibitor–naive

melanoma patients

Reduced incidence of hyperproliferative lesions by

blocking paradoxical activation of the MAPK pathway

from RAF inhibition6

ERK

Uncontrolled proliferation

COT

Increased PDGFRβ/IGF1R activity

RAS mutation

MEK mutation

COT up-regulation

Spliced BRAF isoforms

BRAFiT

MEKiT

CRAF

MEK

BRAFV600

Adapted with permission from AACR.1

RAS

PFS, progression free survival.

Melanom-Hirnmetastasen:

BRAFi + MEKi - Rationale

Therapiestudien bei kutanen

Lymphomen

Jan. P. Nicolay

Studientreffen ADO 2016

Name I Folie 1 I Datum

A Phase 3 Trial of Brentuximab Vedotin(SGN-

35) Versus Physician's Choice (Methotrexate

or Bexarotene) in Patients With CD30-Positive

Cutaneous T-Cell Lymphoma

Brentuximab Vedotin (C25001)

Millennium Pharmaceuticals, Inc. /

Seattle Genetics, Inc.


Studienaufbau C25001

Phase III RCT

Brentuximab-Vedotin i.v. alle 21 Tage

versus

Bexaroten 150 - 300 mg/m² tgl. oder

Methotrexat 5 - 50 mg p.o. wö. (physicians choice)

bei PD im Kontrollarm crossover (SGN-035-10)


Wichtigste Ein- und Ausschlusskriterien

Vorbehandelte (systemisch) Patienten >18 Jahre

n = 124 Patienten

CD30+ großzellig anaplastisches CTCL

CD30+ MF (>10% der Zellen)

CD30+ großzellig transformierte MF


Brentuximab Vedotin (C25001)

Zentren

Berlin

Kiel

Krefeld

Mannheim

Mainz

Minden

Würzburg

LKP:

M. Weichenthal, Kiel

Rekrutierungsstand:

Deutschland: 6

weltweit: 132

1.9.2015 Studie komplett


Pressemitteilung 1.8.2016

Alcanza C25001

ORR4 56.3 % im ADCETRIS-Arm

versus 12.5 % im Bexa/MTX-Arm

p <0.0001

Alle sekundären Endpunkte inclusive Lebensqualität significant besser

Präsentation ASH 12/2016 San Diego


Open-Label, Multi-Center, Randomized Study

of Anti-CCR4 Monoclonal Antibody KW-0761

(Mogamulizumab) Versus Vorinostat in

Subjects With Previously Treated Cutaneous

T-Cell Lymphoma(0761-010)

NCT01728805

Sponsor: Kyowa Hakko Kirin

Pharma, Inc.


Studienaufbau – KW 0761-010

317 Patienten

Vorinostat 400 mg/d

oral

Mogamulizumab

1mg/kg; d1,15

alle 4 Wochen

Ende der Behandlungsphase nach 1 Jahr

Nachbeobachtungsphase 36 Monate

317 Patienten,

open-label, 1:1

randomisiert

Endpunkte:•PFS

•Response rate

•QoL

•Pruritus

•DoR

•Immunogenizität und

Sicherheit von

Mogamulizumab



Einschlusskriterien:•Histologisch gesicherte Mycosis fungoides oder Sézary-Syndrom (CTCL Stadium

≥ Ib) bei Studieneinschluss

•ECOG 0-1

•Vorbehandlung mit topischen oder systemischen CTCL-Therapien bis <28 Tage

vor Studienbeginn (mind eine Vortherapie muss erfolgt sein)

Ausschlusskriterien:•Schwere Systemerkrankung oder Organdysfunktion

•Vortherapie mit Mogamulizumab oder Vorinostat

•Kontraindikation für eine Therapie mit Mogamulizumab oder Vorinostat

•Schwangere oder stillende Patientinnen, Patienten <18 Jahre


Timelines

Studienstart: 11/2012

Rekrutierungsende: 11/2015

Studienende: 2019

Geplante Datenveröffentlichung: 2019


Aktuelle Zahlen

Teilnehmende Zentren:

•Weltweit 73 Zentren

•2 Zentren in Deutschland:

• Mannheim

• Münster

Rekrutierung komplett (373 Patienten)



Name: Marietta Keckeis

E-Mail: [email protected]

Telefonnummer: +49(0) 172 8571 637



Phase IIA Study on Therapy With the NF-κB

Inhibiting and Apoptosis Inducing Drug

Dimethylfumarate (DMF) in Patients With

Cutaneous T Cell Lymphoma (CTCL)(EudraCT-Number: 2014-000924-11)

NCT02546440

IST-Sponsor: Medizinische

Fakultät Mannheim/Heidelberg


Studienaufbau – CTCL DMF

25 Patienten,

einarmiges Design

Endpunkte:•Reduktion des mSWAT

•Reduktion des Juckreizes

•DLQI

•Blutbeteiligung (bei St. IV)




≥ Ib) bei Studieneinschluss mit therapieresistenter, progressiver Erkrankung oder

Rezidiv

•Vorbehandlung mit topischen oder systemischen CTCL-Therapien bis <28 Tage

vor Studienbeginn (mind eine Vortherapie muss erfolgt sein)

Ausschlusskriterien:•Weitere maligne Erkrankungen

•Vortherapie mit DMF oder gleichzeitige topische DMF-Behandlung

•Kontraindikation für eine Therapie mit DMF



Timelines


Studienende: Ende 2018

Geplante Datenveröffentlichung: September

2019/ADO-Tagung


Aktuelle Zahlen

Teilnehmende Zentren (Rekrutierungszahl):

•Mannheim (4/25)

•Kiel

•Krefeld (1/25)

•Ludwigshafen

•Minden (1/25)

•Würzburg



LKP und Sponsorvertreter: Jan Nicolay


Telefonnummer: 0621-3832280



A multicentre, double blind, randomised,

placebo-controlled, Phase II trial to evaluate

Resminostat for maintenance treatment of

patients with advanced stage (Stage IIB-IVB)

mycosis fungoides (MF) or Sézary Syndrome

(SS) that have achieved disease control with

systemic therapy – the RESMAIN study

Sponsor: 4SC AG, Martinsried


Studienaufbau - RESMAIN

150 Patienten, doppel-blind, 1:1 randomisiert mit Placebokontrolle

Endpunkte:

•PFS, Response rate, QoL, Pruritus, DoR, AEs




≥ Ib gemäß der EORTC-ISCL Consensus-Klassifikation) bei Studieneinschluss mit

CR; PR oder SD nach mind. einer Vortherapie

•Vorbehandlung mit systemischen CTCL-Therapien bis 2-8 Wochen vor

Studienbeginn (mind eine Vortherapie muss erfolgt sein)

Ausschlusskriterien:•PD oder ZNS-Beteiligung des CTCL

•Schwere kardiale Vorerkrankung

•Kontraindikation für eine Therapie mit HDAC-Inhibitoren



Timelines


Rekrutierungsende: 12/2019

Studienende: noch nicht absehbar

Geplante Datenveröffentlichung: noch nicht

absehbar


Aktuelle Zahlen


•Weltweit 50 Zentren in 10 Ländern geplant

•?? Zentren in Deutschland

Rekrutierung noch nicht gestartet



Sponsor: 4SC, Martinsried; Dr. Daniel Vitt

Telefonnummer: +49 (0)89 7007630

LKP: Prof. Rudolf Stadler

Telefonnummer: +49 (0)571 7904501

Organisation: ICON; Melanie Milde

Telefonnummer: +49 (0)6185 4371251

Email: [email protected]


Merkellzellkarzinom

Prospective randomized trial of an adjuvant

therapy of completely resected Merkel Cell

Carcinoma (MCC) with 3mg/kg BW

Ipilimumab (Yervoy®) every 3 weeks for 12

weeks versus observation

CA184-205 - ADMEC

Universitätsklinik Essen

BMS

ADMEC - Studienaufbau

• Geplante Patienten: 214

• Gruppenzuteilung

– Arm A: Ipilimumab, 3 mg/kg KG Tag 1 (W1),

22 (W4), 43 (W7), 64 (W10).

– Arm B: Beobachtung

• Staging und Follow-up: Gemäß Leitlinien

• Endpunkte: DFS & OS

ADMEC –


• MCC Stage I – III,

• no evidence of disease

• ECOG: 0 and 1

• Adequate hematologic, liver and renal

function

ADMEC – Teilnehmende ZentrenADMEC

Organisation Abteilung Nachname Vorname

Universitätsklinikum EssenKlinik und Poliklinik für Dermatologie, Venerologie und Allergologie

Schadendorf Dirk

Universitätshautklinik Tübingen Hautklinik Garbe Claus

LMU München, Klinik und Poliklinik für Dermatologie und Allergologie

Klinik und Poliklinik für Dermatologie und Allergologie

Berking Carola

Elbeklinikum Buxtehude Dermatologisches Zentrum Mohr Peter

Universitätsklinikum Schleswig-HolsteinKlinik für Dermatologie, Venerologie und Allergologie

Kähler Katharina C.

Universitätsklinik Carl Gustav Carus der Technischen Universität Dresden

Dermatologie Meyer Friedegund

Nationales Centrum für Tumorerkrankungen Universitätsklinikum Heidelberg

Dermatologie Hassel Jessica Cecile

Medizinische Hochschule Hannover Dermatologie Gutzmer Ralf

Charité Dermatologie Kiecker Felix

Gera Dermatologie Kaatz Martin

Münster Hornheide Onkologie Fluck Michael

ADMEC - Aktueller Stand

• Studienstart: September 2014

• Studienende: September 2017

Anzahl Patienten gescreent: 34

Anzahl Patienten randomisiert: 23

Siteno. City Country Opensince Numberofpatientsscreened Firstpatientscreened Lastpatientscreened Numberofpatientsrandomized Firstpatientrandomized Lastpatientrandomized

01 Essen Germany 24.06.14 8 04.09.14 09.09.16 4 28.01.16 23.05.16

02 Buxtehude Germany 09.07.14 1 12.08.15 12.08.15 1 24.08.15 24.08.15

03 Tübingen Germany 02.10.14 5 31.03.15 25.04.16 5 01.07.15 24.05.16

04 Kiel Germany 12.08.14 3 23.02.16 09.08.16 1 10.03.16 10.03.16

05 München Germany 13.10.14 0 0

06 Dresden Germany 09.10.14 4 28.10.14 08.12.15 3 04.11.14 04.11.15

07 Heidelberg Germany 28.07.14 9 14.08.14 04.08.16 5 16.09.14 31.08.16

08 Berlin Germany 07.03.16 0 0

09 Gera Germany 17.02.16 0 0

10 Hannover Germany 11.02.16 3 07.03.16 14.04.16 3 18.04.16 02.06.16

11 Münster Germany 17.12.15 1 08.01.16 08.01.16 1 22.01.16 22.01.16

Summe 34 23

ADMEC - Aktueller Stand

• Studienstart: September 2014

• Studienende: September 2017



ADMEC – Weiteres Vorgehen

• Verlängerung der Rekrutierungszeit

• Erweiterung der Zahl der Zentren auf 20

• Fallweise Übernahme der Fahrtkosten

A Phase II study of the tumour-targeting

human F16IL2 monoclonal antibody-

cytokine fusion protein in combination with

paclitaxel versus

paclitaxel alone in patients with Merkel cell

carcinoma

IMMOMEC

Philogen

European Commission

IMMOMEC - Aktueller Stand

• Studienstart: Oktober 2013

• Rekrutierungsende: Juni 2016

• Studienende: Dezember 2016



• Data Lock: Dezember 2016

JAVELIN MCC 200

A Phase II, open-label, multicenter trial to

investigate the clinical activity and safety

of MSB0010718C (avelumab) in subjects

with Merkel cell carcinoma

EMD Serono

TCR

T Cell

Tumor

Cell

MHC

Activated

Activation

PD-1

PD-L1

Anti-PD-L1 for advanced MCC

• Phase II, single arm of avelumab

10 mg/kg q2wks as second line

therapy

• Multicenter US and Europe

• PI: Howard Kaufman, Rutgers

University

• ClinicalTrials.gov identifier:

NCT02155647

Javelin MCC 200 - Rekrutierung

Von: Foley, Grace [email protected]

Betreff: Follow-up - with Pfizer/Merck - Expert in MCC session meeting in Frankfurt Tuesday 20th September and Advisory

Board in Berlin Wednesday 23rd November

Datum: 7. September 2016 um 09:21

An: Becker Jürgen C. ([email protected]) [email protected]

Dear Jürgen,

I hope you enjoyed the rest of your weekend. It was great to meet you in person in Vienna and to chatfurther about the ‘Expert in MCC’ session and also the MCC Advisory Board in November in Berlin.

The Meet the expert session in Frankfurt – Tuesday 20th September- It will take place at the Leonardo Royal Hotel Mailänder Straße 1, 60598 Frankfurt - MAP

- I can confirm that your session will start at 17:30 -19:00 on Tuesday 20th September followed by

dinner.

- We have also reserved a room for the night of 20th September in the hotel.

In relation to the content of the presentation, as mentioned if you can share your slides on Friday 16th or

Monday 19th we would appreciate this.

We unfortunately do not have any specific cases on file that could be used other than the case presented atthe symposium.We are looking to collate them in the future but do not have a bank of cases available at the moment.

You mentioned that you may be able to obtain some cases from your colleagues. I list some information

below that I have to date, which includes a list of investigators/sites that have at least enrolled twopatients in the study. It has not been fully verified so apologies in advance if it is not fully accurate but it

may be helpful for you in collating a case study.

UNITED STATES Russell, Jeffrey (Moffitt) 8

UNITED STATES Kaufman, Howard 7

UNITED STATES Hamid, Omid 7

UNITED STATES Bhatia, Shailender 7

GERMANY Terheyden, Patrick 5

UNITED STATESD'Angelo, Sandra

(MSKCC)5

UNITED STATES Shih, Kent (Tenn) 4

FRANCE Lebbe, Celeste 3

UNITED STATES Linette, Gerald (Wash) 3

ITALY Milella, Michele 3

UNITED STATES Brownell, Isaac (NCI) 3

UNITED STATES Lewis, Karl (CO) 3

ITALY Buzzoni, Roberto 2

FRANCE Robert, Caroline 2

UNITED STATES Ferrarotto, Renata (MDA) 2

AUSTRALIA Hill, Andrew 2

FRANCE Mortier, Laurent 2

ITALY Ascierto, Paolo 2

JAPAN Yamazaki, Naoyo (NCI) 2

Reponses to Avelumab

Javelin MCC 200 – 1st Line Extension

TCR

T Cell

Tumor

Cell

MHC

Activated

Activation

PD-1

PD-L1

• Phase II, single arm of avelumab

10 mg/kg q2wks as first line

therapy

• Multicenter US and Europe

• PI: Howard Kaufman, Rutgers

University

• ClinicalTrials.gov identifier:

NCT02155647

• Currently open European sites:

Anti PD-1 for advanced MCC

TCR

T Cell

Tumor

Cell

MHC

Activated

ActivationPD-1

PD-L1

• Multicenter, Phase II, single arm

of pembrolizumab, 2mg/kg q3wks

as first line therapy

• PI: Paul Nghiem and the Cancer

Immunotherapy Trials Network

(CITN), CTEP

• ClinicalTrials.gov Identifier:

NCT02267603

Responses are Independent of

Viral or PD-L1 Status

BMS CA 209-358 (Nivo)

Non-Comparative, Two-Cohort, Single Arm,

Open-Label, Phase 1/2 Study of Nivolumab

(BMS-936558) in Subjects with

Virus-positive Solid Tumors

ClinicalTrials.gov - NCT02488759

Cohort A (Biopsy / Neoadjuvant): 84 subjects prior to surgery

Cohort B (Metastatic): 115 subjects with recurrent or metastatic

disease who have had one prior line of therapy for recurrent or

metastatic disease


• Safety and tolerability of neoadjuvant nivolumab in

patients with resectable tumors:– HPV-positive SCCHN, EBV related gastric cancer, Merkel Cell Carcinoma, HPV

positive cervical/vulvar cancers

• Investigator-assessed objective response rate (ORR) of

nivolumab:

– EBV-related Nasopharyngeal or Gastric carcinoma, Merkel Cell

Carcinoma, HPV positive cervical/vulvar cancers, HPV positive

Squamous Cell cancer of the Head and Neck (SCCHN)

• Active Centers in Germany– University Hospital Essen; Site 0027; Contact: Dirk Schadendorf,

Site

– Klinikum Am Gesundbrunnen Heilbronn; Site 0028; Contact:

Uwe Martens


SYNOPSIS REVIEW PACKAGE

(THIS DOCUMENT IS INTENDED FOR INTERNAL USE ONLY AND IS NOT TO BE DISTRIBUTED EXTERNALLY)

Page 4 of 19

This document is considered Bristol-Myers Squibb Company confidential information.

The information herein may not be disclosed or distributedwithout Bristol-Myers Squibb Company’s Prior approval.

Version Date: 06-Feb-2012

Document Owner: Shawn Pelletier

3.1.1.1 Viral status determination prior to entry

For the neoadjuvant arm, patients enrolled in the Gastric and SCCHN cohorts will be tested for

EBV and HPV, respectively, prior to administration of study drug. For each gastric and SCCHN

cohort, 16 patients with virus positive disease and 5 with virus negative disease will be enrolled.

No prior screening for HPV Gyn or MCC cohorts is necessary due to the high prevalence of viral

positivity and the technical aspects of the MCPyV assay. Viral positivity will be collected

retrospectively in the MCC and GYN cohorts.

Table 7.1.1.1-1: Testing for viral status prior to treatment

Arm Tumor Type Viral status required prior to study drug (Testing)

Neoadjuvant EBV Gastric YES (EBER)

HPV SCCHN YES (HPV 16 in situ hybridization,

Proposed Trial Design

Tumor Types•EBV Gastric•HPV SCCHN •HPV GYN (cervical/vulvar)•M CC

Screening Treatment

Bio

psy

/Ne

oA

dju

van

t

Follow-Up

Me

tast

atic

Up to 4 weeks

ORR

Tumor Types•EBV NPC•EBV Gastric•HPV SCCHN•M CC•HPV GYN (cervical/vulvar)

Treatment Options•Standard of Care † or •Nivolumab ‡ 3 mg/kg IV q14 days untiltoxicity or progression if medically eligible (i.e. meet criteria for metastatic cohort)

Nivo M onotherapy3mg/kg Q2wk

Until toxicity or progression

M in 12 weeks

SurvivalM ax 3 years

M in 12 weeks

• ≥ 1 priortreatment for m etastaticdisease

• ≥ 1 targetlesion

• ECOG PS: 0-1

•Imaging every 6 weeks startingat week 6 for the first year of

treatment. •Imaging every 12 weeks starting

at year 2 and beyond

Biopsy(Prior to 1st dose)

Nivo M onotherapy

3mg/kg x 2 doses

10 subjects ≥ S afety analysis ≥Addtional 6 subjects if ≥ 2 /10 have surgery delayed > 6 weeks due to AE

Biopsy or Surgical

Resection(Day 28)

N=16 with Virus + for each tumor typeN=5 with Virus – for each tumor type except MCC

Subsequent Treatment

N=23 for each tumor type

On-Treatment Assessment

online

Merkelzellkarzinomregister

der ADO

MCC-Register

finanzielle Unterstützung: keine

MCC-Register: Studienaufbau

• Versorgungsforschung

• prospektive und retrospektive Erfassung

– Tumordaten

– Therapie

– Verlauf

• aktuell: 1036 Erstmeldungen, 479 mit F/U

• Zukünftig:

– Histologische Zweitbegutachtung und

zusätzliche prognostische Marker

ZDOZentrum für Dermatoonkologie

Universitäts-Hautklinik TübingenPD Dr. med. Ulrike Leiter

18.06.16

Ulrike LeiterCentre of Dermato-Oncology

University of Tuebingen, Germany

Neue Studie beim epithelialen Tumoren

Plattenepithelkarzinom

A Phase II Study of REGN 28010, a Fully Human MonoclonalAntibody to PD-1 in Patients with Advances Cutaneous Squamouscell carcinoma

2 Gruppen

Group 1 Patients with metastatic CSCC: to distant sites or lymph nodes

Drug: REGN2810

Group 2 Patients with unresectable locally advanced CSCC

Drug: REGN2810


Primary Outcome Measures: • Overall Response Rate During 12 treatment cycles (96 weeks)• Overall Response Rate as determined by RECIST 1.1 for Group 1

and/or assessed per composite response criteria (Group 2)

Secondary Outcome Measures: • Duration of response• PFS• Overall Survival • Change in scores of patient reported outcomes on EORTC QLQ-

C30


Key Inclusion Criteria:• >18 years of age• At least 1 measurable lesion• (ECOG) performance status ≤1• Adequate bone marrow function• Adequate renal function• Adequate hepatic function• Archived or newly obtained tumor material• Patients must consent to undergo biopsies of externally visible

CSCC lesions (Group 2 only)• Surgical or radiological treatment of lesions contraindicated


Key Exclusion Criteria:• Autoimmune disease, ongoing or recent ( 5 years) that required

treatment with systemic immunosuppressive treatments• Prior treatment with an agent that blocks the PD-1/PD-

L1pathway• Prior treatment with a BRAF inhibitor• Prior treatment with other immune modulating like CTLA-4, 4-

1BB (CD137), or OX-40.• Untreated brain metastasis (considered as active)• Immunosuppressive corticosteroid doses (>10 mg prednisone /d)

within 4 weeks prior to the first dose of REGN2810• HIV and/or chronic/active infection Hepatitis B or C virus


Key Exclusion Criteria:• History of pneumonitis within the last 5 years• Allergic reactions attributed to antibody treatments• Known allergy to doxycycline or tetracycline• Patients with a history of solid organ transplant• Any medical co-morbidity, physical examination finding, or

metabolic dysfunction, or clinical laboratory abnormality that renders the patient unsuitable

• Other protocol-defined inclusion/exclusion criteria may apply


Ansprechpartner : Prof. Hauschild, Kiel

Estimated Enrollment: 129Study Start Date: March 2016 jetzt Herbst 2016Estimated Study Completion Date: May 2019Estimated Primary Completion Date: May 2019


Studienstart• Herbst 2016

Teilnehmende Zentren: • Essen• Kiel • Frankfurt• Berlin Charité• Dresden• Hannover• Tübingen

https://clinicaltrials.gov/show/NCT02760498

Weitere Studien mit dieser Substanz der Firma Regeneron sind fürdas

• Merkelzellkarzinom• Basalzellkarzinom

im nächsten Jahr geplant.

Europ. PI: Prof. Hauschild, Kielbei Fragen gerne kontaktieren

Basalzellkarzinom

1. Non-Interventional study to investigate the effectiveness, Safety and utilization of Vismodegib on locally advanced and symptomatic metastastic basal cell carcinoma under real world CONDITIONS (NIELS)• Patienten , die bis 30.3.16 ihre 1. Gabe Vismodegib erhalten

haben, können hier noch eingeschlossen werden

2. Vismodegib on Locally Advanced and Metastatic Basal Cell Carcinoma Under Real World Conditions (JONAS)Folgeprojekt

Sponsor:University Hospital, Essen Collaborator:OnkoDataMed GmbH

Basalzellkarzinom

https://clinicaltrials.gov/show/NCT02781389

Teilnehmende Zentren: • Alle am ADOREG teilnehmenden Zentren

Estimated Enrollment: 53Study Start Date: May 2016Estimated Study Completion Date: April 2020Estimated Primary Completion Date: April 2020

Basalzellkarzinom

JONASPrimary Outcome Measures: • duration of response (partial or complete) until progression,

death or up to 3 years from first dose Vismodegib

Secondary Outcome Measures: • objective response rate, time to response, disease control rate,

recurrence rate, time to progression , survival

Basalzellkarzinom Inclusion Criteria:• Willing and able to provide informed consent• Age ≥ 18 years• laBCC (inappropriate for surgery or radiotherapy)• mBCC (histologic confirmation of distant BCC metastasis)

(including symptoms of metastases e.g. pain, fatigue, disturbed sleep, lack of appetite, nausea/vomiting, shortness of breath, disturbed remembering, dry mouth and coughing will be documented)

• Patient is not included in any other trial• Male or female patient is included in the pregnancy prevention

program, as determined by the German authority (BfArM)

Basalzellkarzinom Exclusion Criteria:• Patients, for whom treatment with Vismodegib is contraindicated

according to the Summary of Product Characteristics (SmPC), which has been in effect at the time of treatment with Vismodegib, including:

• Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. of the latest SmPC

• Women who are pregnant or breast-feeding• Women of childbearing potential who do not comply with the

Vismodegib (Erivedge) Pregnancy Prevention Programme• Coadministration of St John's wort (Hypericum perforatum)

Basalzellkarzinom

A PHASE II, SINGLE-ARMED, MULTICENTER TRIAL OF NEOADJUVANT VISMODEGIB IN PATIENTS WITH LARGE AND/OR RECURRENT BASAL CELL CARCINOMANICCI

A PHASE II, SINGLE-ARMED, MULTICENTER TRIAL

OF NEOADJUVANT VISMODEGIB IN PATIENTS

WITH LARGE AND/OR RECURRENT RESECTABLE

BASAL CELL CARCINOMA

NICCI

Martin Kaatz

SRH Wald-Klinikum Gera GmbH

Straße des Friedens 122

D-07548 Gera

247

StudienaufbauGeplante Patientenanzahl:

• 65 Patienten

Gruppenzuteilung:

• keine/ nicht randomisiert

Therapieschema:

• 3 Zyklen a 28 Tage mit 150mg Vismodegib

Primäre Endpunkte:

• Bewertung der Krankheitskontroll-Rate (DCR)

• Auswertung der objektiven und relativen (%)

Reduktion der betroffenen Hautoberfläche

248

Studienaufbau

249

Wichtigste Einschlusskriterien

- Patient hat wenigstens ein großes BCC:

≥ 2 cm im Durchmesser im Kopf-/Hals-Bereich oder

≥ 5 cm an Rumpf/Extremitäten

- Histologisch gesicherter Befund

- Optional: Durchführung von nichtinvasiven bildgebenden

Untersuchungen mittels konfokaler Laserscanmikroskopie

(CLSM) und/oder optischer Kohärenztomographie (OCT)

während und nach Beendigung der Studienbehandlung

250

251

Wichtigste Ausschlusskriterien

- maximal eine Radiotherapie der Zielläsion(en) erlaubt,

(mindestens 6 Monate vor Registrierung abgeschlossen)

- Vorbehandlung mit einem Hedgehog-Inhibitor

- Metastasiertes Basalzellkarzinom

- Metatypisches Basalzellkarzinom

- Bekanntes oder vermutetes Gorlin-Goltz-Syndrom

252

Timelines

Einreichung: 16.09.2016

Einschluss des ersten Patienten (FPI): Q4 / 2016

Einschluss des letzten Patienten (LPI): Q4 / 2017

Ende der Behandlung (LP off treatment): Q1 / 2018

Ende der Nachbeobachtung (LP off study): Q1 / 2019

253

10 Prüfzentren• SRH Wald-Klinikum Gera GmbH

• Universitätsklinikum Tübingen

• Charité - Universitätsmedizin Berlin

• Elbe Kliniken Stade - Buxtehude GmbH

• Klinikum Augsburg Süd

• Klinikum Nürnberg Nord

• Universitätsklinikum Heidelberg

• Universitätsmedizin Rostock

• Universitätsklinikum Münster

• Fachklinik Hornheide254

Ansprechpartner

LKP: PD Dr. med. habil. Martin Kaatz

Medical: Sabine Sell, OÄ Beatrice Schell, Julia Feld

PM, IMP: Dr. Claudia Deumer

OCT, CLSM: Dr. Michael Zieger

Zentral erreichbar über:


Tel.: +49 (0) 365 / 828 77 58

255

256

Aufbau und Betrieb eines prospektiven

Registers zur Versorgungsforschung in der

dermatologischen Onkologie

ADOREG

Arbeitsgemeinschaft Dermatologische

Onkologie

LeitungsgruppeGarbe, Reimer,. Schadendorf,

Hansen, Weichenthal

Akademischer

ProjektbeiratUgurel, Augustin, Berking,

Gutzmer, Weichenthal

Projektleitung Basissoftware Leiter, Hansen, Plötner, Weichenthal

Wiss. Beirat

DKG DDG ADOKatalinic Enk Grabbe

beaufsichtigt

berichtet

Pharmazeutische

ProjektgruppeAlmirall Amgen, BMS, Leo,

Medac, Novartis, Roche

ADOREG-- Steuerung, Lenkung sowie Beteiligung – (Stand 06/2015)

berätformuliert

Anforde-rungen

Projekt 1

Leitung

Projekt 2

Leitung

Projekt n

Leitung

A B C D E F NG H

Zentren Definiert

Studien,

ernennt

Leitung

ber

ich

tet

berät/betreut

formuliert Anforde-

rungen

Trustcenter

Hochschule Heilbronn

Berät

Schlägt vor

ADOREG-Datenschutzkonzept

ADOREG-Zentrenstatus

• 40 aktive Zentren

• 8 weitere Verträge in Verhandlung bzw. in

Zeichnungsumlauf

• Interesse österreichischer Kliniken

Status Patienteneinschlüsse

09/2016

Entität Anzahl Patienten

MM 1.471

BCC 133

Gesamtzahl Patienten 1.632

ADOReg Rekrutierung

ADOReg Melanomfälle

Klinisches Stadium Anzahl Patienten

0 9

IA 12

IB 18

II 3

IIA 32

IIB 60

IIC 48

III 7

IIIA 80

IIIB 154

IIIC 166

IV 854

https://qs.adoreg.de/quasi/industrie

https://qs.adoreg.de/quasi/industrie

Status Teilregister epitheliale

Tumoren

• BCC-Register fertig programmiert und

getestet, aktuell 133 Fälle

• Freischaltung für die Zentren seit Oktober

2015

Aktuell:

Planung SCC-Register

Vorplanungen MCC-Register

Vorbereitung AK-Register

ADO-Reg PEM

Now

Combi-R

ADOReg

„NIS meets Register“

PemNow

PemNow

• Studienleiter: Dr. Peter Mohr, Buxtehude

• Geplante Patienten: 400

• Einschluss:

nach 1.3.2015 unter Behandlung mit

Pembrolizumab EAP oder nach Zulassung

• Gesonderte Honorierung zusätzlich zur

ADOReg-Basishonorierung

• Kontakt: [email protected]

PemNow

• 08/2016

• Eingeschlossene Patienten: 405

• Geplante Aufstockung auf 550 Patienten

• Budget für Dokumentation in Verhandlung

• Rekrutierung „on hold“

Anzahl teilnehmender (aktiver) Zentren

Anzahl

eingeschlosse

ner Patienten

Anzahl

vollständiger Patienten

27 405 201

Sponsor: Novartis

COMBI-r, eine nicht-interventionelle Studie bei Patienten mit fortgeschrittenem Melanom zur Bewertung der

Kombinationstherapie mit Dabrafenib und Trametinib in der klinischen Routine (DRB436BDE04)

Juli 2016

https://awbdb.bfarm.de/ords/f?p=101:20:::NO , BfArM: Nr. 6690

https://awbdb.bfarm.de/ords/f?p=101:20:::NO

COMBI-rKombinationstherapie Dabrafenib+Trametinib in der klinischen Routine

Dokumentationszeitraum 12/2015 –

06/2019Wichtigste Ziele

• Effizienz & klinischer Nutzen

• Sicherheit & Verträglichkeit

• Lebensqualität (QoL)

• Korrelation Biomarker & klinischer

Parameter mit klinischem

Nutzen

• Therapie-Sequenz vor/nach Therapie

• Dauer der Therapie & Therapie-

Management

• Methoden der BRAFV600-

Mutationsanalyse




Patientendaten, die in COMBI-r dokumentiert wurden, können in das ADOREG –

Register überführt werden und so zusätzlich einer unabhängigen Auswertung

und Nutzung durch die ADO zur Verfügung stehen.

ADOREG

Datentransfer ins ADOREG nach

ausdrücklicher und individueller

Zustimmung des Patienten




Aktuelle Zahlen


48 (Stand August 2015)

bis zu 60 Zentren geplant

Dokumentierte Patienten:

68 (Stand August 2016)

Ansprechpartner

Medical Advisor

(wissenschaftliche Fragen):

Dr. Julia Kleylein-Sohn

0911-27312118

[email protected]

Clinical Research Manager

(Projektmanagement und

wissenschaftliche Fragen):

Antonia Wolff

0151-218 50579

[email protected]

JONAS

Nicht-interventionelle Studie zur Untersuchung der

Wirksamkeit, Sicherheit und Anwendung von

Vismodegib bei lokal fortgeschrittenem und metasta-

sierten Basalzellkarzinom unter realen Bedingungen

LeitungsgruppeGarbe, Reimer,. Schadendorf,

Stiegler, Weichenthal

Akademischer

ProjektbeiratAugustin, Berking,

Gutzmer, Ugurel,

Weichenthal

Projektleitung Basissoftware Leiter, Stiegler, Thielecke, Weichenthal

Wiss. Beirat

DKG DDG ADOKatalinic Enk Grabbe

beaufsichtigt

berichtet

Pharmazeutische

ProjektgruppeAlmirall Amgen, BMS, Leo,

Medac, Novartis, Roche

ADOREG-- Steuerung, Lenkung sowie Beteiligung – (Stand 06/2015)

berätformuliert

Anforde-rungen

Projekt 1

Leitung

Projekt 2

Leitung

Projekt n

Leitung

A B C D E F NG H

Zentren Definiert

Studien,

ernennt

Leitung

ber

ich

tet

berät/betreut

formuliert Anforde-

rungen

Trustcenter

Hochschule Heilbronn

Berät

Schlägt vor

Akademische Projekte in ADOREG

• Zielsetzung

– Projekte / Studien mit akademischer Fragestellung innerhalb des Registers ADOREG

– prospektiv und/oder retrospektiv

– Aktuelles akademisches ADOREG Projekt: TRIM (prospektiv)

– Weitere Projekte geplant nach Antragseinreichung und Beurteilung durch den akademischen Projektbeirat

• Akademischer Projektbeirat

– 5 Mitglieder: Selma Ugurel (Essen) Carola Berking (München), Ralf Gutzmer (Hannover), Matthias Augustin (HH), Michael Weichenthal (Kiel)

• Ablauf

– Einreichung einer Antragsskizze

– Beurteilung der Realisierbarkeit und Finanzierung (vor allem bei prospektiven Projekten)

– Erste Anträge zunächst aus den ADO Kommittees geplant (CIE Translationale Forschung; CIE Nebenwirkungen, CIE Supportivtherapie)

TRIM (Tissue Registry in Melanoma)

• Akademisches Projekt in ADOREG

• Projektleiter: Dirk Schadendorf, Selma Ugurel (Essen)

• Ziele des Projektes

– multizentrische Sammlung von Daten zur molekularen Charakterisierung von Tumorgewebe bei Patienten mit metastasiertem Melanom vor Einleitung einer systemischen Therapie

– Untersuchung der molekularen Parameter als prädiktive / prognostische Marker

• Einschlusskriterien

– Patienten mit metastasiertem Melanom im Stadium III oder IV

– Geplante systemische Therapie in jeglicher Therapielinie

– Tumorgewebe des Patienten als Paraffinmaterial vorhanden (möglichst aktuelles Probenmaterial aus Metastase; älteres Gewebematerial bis hin zum Primärtumor auch möglich)

– Einwilligung des Patienten in Projektteilnahme TRIM und Datenerfassung über ADOREG

• Durchführung

– Registrierung des Patienten über ADOREG

– Versand von Tumorgewebe in Form von Paraffinblock oder Schnitt-präparaten (20 Stück) an Labor der Hautklinik Essen

– Untersuchung der Gewebe auf • Mutationen in 30 Melanom-relevanten Genen mittels Next-Generation-

Sequencing (MiSeq, Illumina)

• PD-L1 Expression mittels Immunhistochemie (PharmDx 28-8 auf DAKO Autostainer)

– Nach 7-14 Tagen Erhalt eines Ergebnisbefundes über ADOREG

• Finanzierung

– Materialkosten übernommen von BMS

– Molekulare Analysen für das Zentrum kostenfrei

– Im Gegenzug Dokumentation der klinischen Daten (Baseline und FollowUp) in ADOREG durch das Zentrum ohne zusätzliche Vergütung

– Basis-Dokumentation der betreffenden Patienten regulär vergütet über ADOREG



Stand vom

05.09.2016:

Aktive Zentren: 12

Eingeschlossene

Patienten: 332

Anzahl der

eingesandten

Gewebeproben: 364

Kontakt:selma.ugurel@uk-

essen.de

[email protected]

• Auswertung– Korrelation der Daten aus molekularer Diagnostik

mit dem klinischen Verlauf der Patienten: prädiktive Aussage bezüglich Therapieansprechen und Überleben ?

– Vergleich mit bekannten prognostischen und prädiktiven Markern des Melanoms

• Anmeldung zum Projekt / Ansprechpartner– über ADOREG

– über Universitäts-Hautklinik Essen:

• LABOR: Antje Sucker ([email protected])

• DATENBANK: Selma Ugurel ([email protected])


Antrag

Review

Formular erarbeiten auf ADO-Reg Webseite

revidierter Antrag

Prereview

Rückfrage

Fragestellung, Datenmenge, evtl. zusätzliche Daten nötig

→ Zentrengezielt ansprechen

negativ Ablehnung

positiv

Leitungsgruppe

Zustimmung

Daten liegen vor

Aufwand/Budget

→ Finanzierung klären

Leitungsgruppe

ZustimmungODM: Daten an

Projektleiter

jageklärt

zusätzliche Datenerfassung/

Auswertung nötig

Auswertung/

Bericht

Datenerfassung,

Zentren

anfragen etc.

jaVoraus-

setzungen

vorhanden

Zeitraum?

Koautorenschaften für Zentren mit vielen Datensätzen

Patienteninfo/-EV 2.5 vom 11.8.2016

NICHT ZU VERWENDUNG ++++ ÜBERARBEITUNG FOLGT

Vielen Dank !

Documents

ADO-Studientreffen Melanom Adjuvant/Neoadjuvant · abdomen and pelvis. ... • Unstable hyperthyroidism or hypothyroidism • Diagnosis of immunodeficiency ... End of study: LPLV