NIHR/Wellcome UCLH Clinical Research Facility · 2 NIHR UCLH Clinical Research Facility News Update New Trials Open to Recruitment BLU-667-1101 - A phase I study of the highly-selective

Cancer Trials Portfolio July 2018

NIHR/Wellcome UCLH Clinical Research Facility

2

NIHR UCLH Clinical Research Facility News Update

New Trials Open to Recruitment BLU-667-1101 - A phase I study of the highly-selective RET inhibitor, BLU-667, in patients with thy-roid Cancer, non-small cell lung cancer (NSCLC) and other advanced solid tumours (PI Dr Forster) GCT1021-01 - First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (Hu-Max-AXL-ADC) in patients with solid tumours (PI Dr Shaw) AZD6738 - A Modular phase I, open-label, multicentre study to assess the safety, tolerability, phar-macokinetics and preliminary Anta-tumour activity of ascending doses of AZD6738 in combination with cytotoxic chemotherapy and/or DNA damage repair/novel anti-cancer agents in patients with advanced solid malignancies (PI Dr Roylance)

Recent Publications Palmer DH, Ma YT, Peck-Radosavljevic M, Ross P, Graham J, Fartoux L, Deptala A, Studeny M, Schnell D, Hocke J, Loembé AB, Meyer T. A multicentre, open-label, phase-I/randomised phase-II study to evaluate safety, pharmacokinetics, and efficacy of nintedanib vs. sorafenib in European patients with advanced hepa-tocellular carcinoma. Br J Cancer. 2018 May;118(9):1162-1168.

ASCO, June 2018 Johnson ML, Meyer T, Halperin DM, Fojo AT, Cook N, Blaszkowsky LS, Schlechter BL, Yao JC, Jemiai Y, Kriksciukaite K, Jones M, Ezema N, Mei L, Alland L, Kulke MH. First in human phase 1/2a study of PEN-221 somatostatin analog (SSA)-DM1 conjugate for patients (PTS) with advanced neuroendocrine tumour (NET) or small cell lung cancer (SCLC): Phase 1 results.

Gaspar N, Casanova M, Sirvent FJB, Venkatramani R, Morland B, Gambart M, Thebaud E, Strauss SJ, Locatelli F, Melcon SG, Nieto AC, Bielack S, RossigC, Aerts I, Marec-Berard P, Kraljevic S, Hayato S, He C, Dutcus C, Campbell-Hewson Q.Single-agent expansion cohort of Lenvatinib (LEN) and combination dose-finding cohort of LEN + Etoposide (ETP) + Ifosfamide (IFM) in patients (pts) Aged 2 to ≤ 25 years with re-lapsed/refractory Osteosarcoma (OS).

Sarker D, Plummer ER, Bristi Basu, Meyer T, Huang K, Evans TRJ, Spalding D, Ma YT, Palmer DH, Chee CE, Habib NA. Preliminary results of a first-in-human, first-in-class phase I study of MTL-CEBPA, a small ac-tivating RNA (saRNA) targeting the transcription factor C/EBP-α in patients with advanced liver cancer.

Bridgewater J, Palmer DH, Ryder D, Gnanaranjan C, Ghazaly EA, Evans TRJ and Valle JW. NUC-1031 combined with cisplatin for the treatment of advanced biliary tract cancer (ABC-08).

1st European Myeloma Network Meeting, Apr 2018 Popat R, Trudel S, Lendvai N, Voorhees P, Reeves B, Libby E, Richardson P, Anderson L Jr, Suther-land H, Yong K, Hoos A, Gorczyca M, Lahiri S, He Z, Jewell R, Opalinska J, Cohen A. Targeting B-cell matu-ration antigen (BCMA) with GSK2857916 antibody-dug conjugate provides responses in patients (PTS) with heavily-pretreated relapsed/refractory multiple myeloma (RRMM): Preliminary results from study BMA117159

New European Drug License Rubraca received conditional marketing authorisation valid throughout the EU on 24 May 2018.

The data generated from CO-338-010 study (A Phase I/II, Open-Label, Safety, Pharmacokinetic, and Pre-liminary Efficacy Study of Oral Rucaparib in Patients with gBRCA Mutation Breast Cancer or Other Solid Tu-mour and ARIEL2 (PI Dr Kristeleit ) have enabled Rucaparib being licensed in US since Dec 2016 and the recent authorisation my EMA.

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How to Refer a Patient By post:

NIHR UCLH Clinical Research Facility,

University College London Hospitals NHS Foundation Trust,

UCLH, 4th Floor, 170 Tottenham Court Road,

London, W1T 7HA

By telephone:

Reception: 020344 72929/72930

Reception Fax: 020344 72994

By email**:

Name Email Dr K Ardeshna [email protected]

Dr J Bridgewater [email protected]

Dr M Forster [email protected]

Prof D Hochhauser [email protected]

Dr R Kristeleit [email protected]

Dr M Linch [email protected]

Prof T Meyer [email protected]

Dr R Miller [email protected]

Dr Papadatos-Pastos [email protected]

Dr R Popat [email protected]

Dr R Roylance [email protected]

Prof R Sharma [email protected]

Dr H Shaw [email protected]

Dr S Strauss [email protected]

Dr W Townsend [email protected]

**When referring patients via non-NHS email accounts please do not include any patient identifiable data

Trial Portfolio Contents

Breast

Gastro-Intestinal

Gynaecological

Haematology

Head and Neck

Hepatobiliary

Lung

Prostate

Sarcoma

Solid Tumours

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Breast

Drug Class / PI / Status Description

Fulvestrant, neratinib + fulvestrant, AZD5363

+ fulvestrant or AZD5363

PI: Dr Rebecca Roylance

Status: Open to recruitment

A multiple parallel cohort, open-label, multi-centre phase IIa clinical trial aiming to provide proof of principle efficacy for designated targeted therapies in patients with advanced breast cancer where the targetable mutation is identified through ctDNA screening

Study acronym: PLASMA MATCH

BET inhibitor + fulvestrant



A phase I/II dose escalation and expansion study to investigate the safety, pharmacokinetics, pharmacodynamics and clinical activity of GSK525762 in combination with fulvestrant in subjects with ER+ breast cancer

Study acronym: GSK525762

CDK4/6 inhibitor



Phase 1/2 safety, pharmacokinetic, and antitumor activity study of G1T38 in combination with Fulvestrant in patients with hormone receptor-positive, HER2-negative locally advanced or metastatic breast cancer after endocrine failure

Study acronym: G1T-38

Protein Kinase inhibitor



A Modular Phase I, Open-Label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics and Preliminary Anti-tumour Activity of Ascending Doses of AZD6738 in combination with Cytotoxic Chemotherapy and/or DNA Damage Repair/Novel Anti-cancer Agents in Patients with Advanced Solid Malignancies

Study acronym: AZD6738

PARP inhibitor

PI: Dr Rebecca Kristeleit

Status: In set-up

A phase IB/II study to evaluate safety and anti-tumour activity of Avelumab in combination with the Poly(adenosine diphosphate (ADP)-ribose) polymers (PARP) inhibitor Talazoparib in patients with locally advanced or metastatic solid tumours

Study acronym: MEDLEY B9991025

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Gastro-Intestinal


First in class nucleotide analogue (ProTide)

PI: Dr John Bridgewater


A phase Ib, multi-centre, open-label study of a first-in-class nucleotide analogue Acelarin (NUC-1031) in combination with cisplatin in patients with locally advanced/metastatic biliary tract cancers

Study acronym: ABC-08

Anti-VEGF

PI: Prof John Bridgewater


A phase I/II dose finding study evaluating the safety and tolerability of Capecitabine and Afilbercept in patients with unresectable metastatic colorectal cancer deemed unsuitable for double/ triplet chemotherapy

Study acronym: CAPITAL

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Gynaecological


PARP inhibitor + anti-PD-L1 Ab

PI: Rebecca Kristeleit


A phase Ib combination study of Rucaparib (CO-338) and Atezolizumab (MPDL3280a) in patients with solid tumours and advanced gynecologic cancers, with a focus on ovarian cancer

Study acronym: COUPLET

TIL therapy


Status: In set-up

A Phase II, multicentre, 3-cohort study to assess the safety and efficacy of Autologous Tumour Infiltrating Lymphocytes (LN-144) in patients with recurrent metastatic, or persistence Cervical Carcinoma

Study acronym: LN-145

CHK1 Inhibitor


Status: In set-up

A Phase I Trial of Oral SRA737 (a Chk1 Inhibitor) Given in Combination with Gemcitabine plus Cisplatin or Gemcitabine Alone in Subjects with Advanced Cancer

Study acronym: SRA737-02 combo

PARP inhibitor


Status: In set-up



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Complement C1 Antibody

PI: Dr William Townsend


Safety, tolerability and activity of TNT009 in healthy volunteers and patients with complement-mediated disorders. A single/multiple ascending dose Phase I study

Study acronym: TNT009-01 part E

BET inhibitor

CI: Dr Rakesh Popat


Open-label, multicentre, dose escalation/expansion Phase Ib study to evaluate safety, pharmacokinetics and activity of BET inhibitor RO6870810, given as mono– and combination therapy to patients with advanced Multiple Myeloma.

Study acronym: NP39403

E-selectin inhibitor

PI: Dr Rakesh Popat


A Phase I Open Label Dose Escalation Study to Determine the Efficacy, Safety and Pharmacokinetics of GMI-1271 as Adjunct to Standard of Care Chemotherapy for the treatment of Multiple Myeloma

Study acronym: GMI -1271

Haematology


Next generation IMiD

PI: Dr Rakesh Popat


A phase IB/2A multicentre, open-label, dose-escalation study to determine the maximum tolerated dose, assess the safety and tolerability, pharmacokinetics and preliminary efficacy of CRL4 Cereblon E3 ubiquitin ligase modulator monotherapy and in combination with dexamethasone in subjects with relapsed and refractory Multiple Myeloma

Study acronym: CC-220

Dual PI3kinase - mTOR inhibitor



Open-label, Non-randomized Phase 2 Study With Safety Run-in Evaluating Efficacy and Safety of PQR309 in Patients with Relapsed or Refractory Lymphoma

Study acronym: PQR309

Small molecule inhibitor


Status: open to recruitment

Phase 2 Study of TAK-659 in Patients With Relapsed or Refractory Diffuse Large B-Cell Lymphoma After at Least 2 Prior Lines of Chemotherapy

Study acronym: TAK-659 phase 2

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Haematology continued


Antibody drug conjugate targeting BCMA

PI: Dr Rakesh Popat

Status: Open to recruitment (DLBCL cohort)

A phase I open-label, dose escalation study to investigate the safety, pharmocokinetics, pharmacodynamics, immunogenicity and clinical activity of the antibody drug conjugate GSK2857916 in subjects with relapsed/refractory multiple myeloma and other advanced hematologic malignancies expressing BCMA

Study acronym: BMA117159

ATR inhibitor


Status: In set-up

Phase 1-2 proof-of-concept study investigating AZD6738 (ATR inhibitor) given as monotherapy and in combination with Acalabrutinib in subjects with relapsed/refractory High-risk CLL

Study acronym: Acerta

Bi-specific antibody


Status: In set-up

A phase IB study evaluating the safety and pharmacokinetics of RO7082859 in combination with an anti-CD20 targeting agent (Obinutuzumab [G] or Rituximab [R]) plus Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone (CHOP) in Patients with relapsed refractory indolent Non-Hodgkin’s Lymphoma (r/r iNHL) or in patients with diffuse large B-cell lymphoma

Study acronym: NP40126

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Head and Neck


PARP-1 inhibitor

PI: Dr Martin Forster


A phase I study of Olaparib in addition to Cisplatin-based concurrent chemoradiotherapy for patients with high risk locally advanced squamous cell carcinoma of the head and neck (HNSCC)

Study acronym: ORCA2

WEE 1 inhibitor



A Phase I trial of WEE1 inhibition with chemotherapy and radiotherapy as adjuvant treatment, and a window of opportunity trial with Cisplatin in patients with Head and Neck cancer

Study acronym: WISTERIA

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Hepatobiliary


FGFR4 inhibitor

PI: Prof Tim Meyer


A phase I study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of BLU-554 in patients with hepatocellular carcinoma and cholangiocarcinoma

Study acronym: HCC BLUE

Small activating RNA (saRNA)

PI: Prof Tim Meyer


Phase I clinical study with RNA oligonucleotide drug MTL-CEBPA to investigate its safety and tolerability and to ascertain whether MTL-CEBPA mediated up-regulation of CEBPA gene expression is associated with increase in serum albumin in patients with advanced hepatocellular carcinoma or patients presenting with secondary liver tumours derived from extra hepatic primary cancer types.

Study acronym: OUTREACH

Multi kinase inhibitor

PI: Prof Ricky Sharma


VEROnA: A pilot, open label, single-arm, phase 0, window of opportunity study of vandetanib-eluting radiopaque embolic beads (BTG-002814) in patients with resectable liver malignancies

Study acronym: VEROna

T Cell therapy

PI: Prof Tim Meyer


A Phase I open label, clinical trial evaluating the safety and anti-tumor activity of Autologous T Cells expressing enhanced TCRs specific for alpha-fetoprotein (AFPc332T) in HLA-A2 positive subjects with advanced Hepatocellular Carcinoma (HCC)

Study acronym: Adaptimmune

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Lung


Second Generation Hypo-Methylating Agent

PI: Dr Dionysis Papadatos-Pastos


HyPeR: A Phase 1, Dose Escalation Study of Guadecitabine (SGI-110) a Second Generation Hypo-Methylating Agent in Combination with Pembrolizumab (MK3475) in Patients with Refractory Solid Tumours

Study acronym: HyPer

Prostate


PARP inhibitor


Status: In set-up



Glucocorticoid receptor (GR) antagonist

PI: Dr Mark Linch

Status: In set-up

Phase I/II dose-escalation and expansion study to evaluate the safety, tolerability, and pharmacokinetics of CORT125281 with enzalutamide in patients with metastatic castration-resistant prostate cancer

Study acronym: CORT125281

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Sarcoma


PARP-1 inhibitor

PI: Dr Sandra Strauss


A Phase I Study of a Combination of the PARP Inhibitor, Niraparib and Temozolomide or Irinotecan in Patients with Previously Treated, Incurable Ewing Sarcoma

Study acronym: ESPIRIT

Receptor tyrosine kinase (RTK) inhibitor



Phase 1/2 Study of Lenvatinib in Children and Adolescents With Refractory or Relapsed

Solid Malignancies and Young Adults with Osteosarcoma

Study acronym: EISAI

EGFR small molecule inhibitor


Status: In set-up

A phase 2, single arm, European multi-centre trial evaluating the efficacy of Afatinib as first-line or later-line treatment in advanced Chordoma.

Study acronym: Afatinib in Chordoma

Anti PD-1 and Tyrosine kinase inhibitor


Status: In set-up

Phase I-II trial of sunitinib plus nivolumab after standard treatment in advanced soft tissue and bone sarcomas

Study acronym: ImmunoSARC

CHK1 Inhibitor


Status: In set-up



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Solid Tumours


Autologous γδ T Lymphocyte Therapy



An adaptive study of the safety, tolerability and efficacy of autologous γδ T Lymphocyte therapy in patients with advanced cancers which are refractory to current treatment or who have indolent disease for which immunotherapy may be beneficial

Study acronym: IMMUNICELL

Small molecule



A multicentre phase II clinical trial of Lurbinectedin in selected advanced solid tumours.

Study acronym: PM BASKET

PARP inhibitor + anti-PD-L1 Ab

PI: Rebecca Kristeleit


A phase Ib combination study of Rucaparib (CO-338) and Atezolizumab (MPDL3280a) in patients with solid tumours and advanced gynecologic cancers, with a focus on ovarian cancer

Study acronym: COUPLET

Anti–OX40 antibody



A phase I/II, open-label, dose-escalation, safety and tolerability study of INCAGN01949 in subjects with advanced or metastatic solid tumours.

Study acronym: OX40

Hu-Max-AXL-ADC

PI: Dr Heather Shaw


First-in-human, open-label, dose-escalation trial with expansion cohorts to evaluate safety of Axl-specific antibody-drug conjugate (Hu-Max-AXL-ADC) in patients with solid tumours

Study acronym: GCT1021

Biologic Drug Conjugate

PI: Prof Tim Meyer


A phase I/IIa, open-label multicentre study to assess the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of a biologic drug conjugate in patients with somatostatin receptor 2 expressing advanced cancers, including gastroenteropancreatic or lung or thymus or other neuroendocrine tumours or small cell lung cancer or large cell neuroendocrine carcinoma of the lung

Study acronym: PEN-221 Tarveda

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Solid Tumours continued


PI3K Inhibitor

PI: Dr Mark Linch


A phase I, open-label, multicentre study to assess the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary anti-tumour activity of AZD8186 in patients with advanced castration-resistant prostate cancer (CRPC), squamous non-small cell lung cancer (sqNSCLC), triple negative breast Cancer (TNBC) and patients with known PTEN-deficient/mutated or PIK3CB mutated/amplified advanced solid malignancies, as monotherapy and in combination with Abiraterone Acetate or AZD2014

Study acronym: AZD-8186

ATR kinase inhibitor



A phase I study to assess the tolerability, safety and biological effects of a specific Ataxia Telangiectasia and Rad3-related (ATR) inhibitor (AZD6738) as a single agent and in combination with palliative radiation therapy in patients with solid tumours

Study acronym: PATRIOT

Anti-PD-1

PI: Prof Tim Meyer


Non-comparative, two-cohort, single-arm, open-label, phase I/II study of Nivolumab (BMS-936558) in subjects with virus-positive and virus-negative solid tumours

Study acronym: BMS CA209-358

Anti-androgen 10-amino acid peptide


Status: Open to recruitment (Prostate only)

A phase I/II, dose escalation study to assess the safety and tolerability of VAL201 in patients with locally advanced or metastatic prostate cancer and other advanced solid tumours

Study acronym: VAL201-001

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TRK Inhibitor



A Phase II Basket Study of the Oral TRK Inhibitor LOXO-101 in Subjects with NTRK Fusion-Positive Tumors

Study acronym: LOXO

Anti folate receptor-α Ab



Phase I study of MOv18 IgE, a first in class chimeric IgE antibody against folate receptor-α, in patients with advanced solid tumours

Study acronym: MOv18

Anti PD-L1



A Phase I Dose Escalation and Cohort Expansion Study of an anti-PD-1 Monoclonal Antibody, in Patients with Advanced Solid Tumors

Study acronym: GARNET

CHK1 Inhibitor



A Phase I trial of SRA737 (a CHK1 inhibitor) administered orally in subjects with advanced cancer .

Study acronym: SRA737-01 mono

MET receptor tyrosine kinase inhibitor



A modular, multi-arm, multi-part, first time in patient study to evaluate the safety and tolerability of OMO-1, alone and in combination with anti-cancer treatments, in patients with locally advanced, unresectable or metastatic solid malignancies

Study acronym: OCTIMET

RET inhibitor



A phase I study of the highly-selective RET inhibitor, BLU-667, in patients with Thyroid cancer, non-small cell lung cancer (NSCLC) and other advanced solid tumours

Study acronym: BLU667

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Arginase inhibitor



A Phase 1/2 Study to Evaluate the Safety, Tolerability, and Efficacy of INCB001158 in Combination With Chemotherapy, in Subjects With Advanced or Metastatic Solid Tumours

Study acronym: INCB 01158-203 Arginase

Microtubule inhibitor



An open-label Phase 1/2a study of oral BAL101553 in adult patients with advanced solid tumors and in adult patients with recurrent or progressive glioblastoma or high-grade glioma.

Study acronym: Basilea Oral

FGFR Inhibitor

PI: Dr John Bridgewater


A dose finding Phase I study of TAS-120 in patients with advanced solid tumours with or without Fibroblast Growth Factor/receptor (FGF/FGFR)- related abnormalities followed by a Phase II study in patients with advanced solid tumours FGF/FGFR-related abnormalities

Study acronym: TAS120-101

Tubulin polymerase inhibitor



A Phase I/II dose escalation study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of DTX-SPL8783 (a docetaxel (DTX)-dendrimer conjugate) as monotherapy in patients with advanced solid tumours or in combination with Nintenadib in patients with n0n-small cell lung cancer (NSCLC)

Study acronym: Starpharma DTX

TIL therapy


Status: In set-up

A Phase II, multicentre, 3-cohort study to assess the safety and efficacy of Autologous Tumour Infiltrating Lymphocytes (LN-144) in patients with recurrent metastatic, or persistence Cervical Carcinoma


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Drug-dendrimer conjugate


Status: In set-up

A phase I/II dose-escalation study to evaluate the safety, tolerability, pharmacokinetics and preliminary efficacy of CTX-SPL9111 (a cabazitaxel (CTX)-dendrimer conjugate) in patients with advanced solid tumours

Study acronym: Starpharma CTX

BET Inhibitor


Status In-Set Up

A phase I//IIa trial with BMS986158, a small molecule inhibitor of the Bromodomain and Extra-Terminal (BET) proteins in subjects with selected advanced solid tumours.

Study acronym: BMS—986158

PARP inhibitor


Status: In set-up



CHK1 Inhibitor


Status: In set-up



Anti PDK7 Antibody

PI: Dr Rowan Miller

Status: In set-up

A first in human Phase I, dose escalation, safety and pharmacokinetic study of B7661001 in adult patients with advanced solid tumours

Study acronym: B7661001

TIL therapy

CI: Dr Heather Shaw

Status: In set-up

A phase II, multicentre, 3-cohort study to assess the safety and efficacy of Autologous Tumour Infiltrating Lymphocytes (LN-144) for treatment of patients with Metastatic Melanoma


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Documents

NIHR/Wellcome UCLH Clinical Research Facility · 2 NIHR UCLH Clinical Research Facility News Update New Trials Open to Recruitment BLU-667-1101 - A phase I study of the highly-selective