Immunotherapy in Gynaecological cancers -...

Immunotherapy for Gynaecological (Breast and

Ovarian) CancersESMO Immunotherapy Preceptorship

Singapore 2017

David SP Tan, MD PhD FRCP

Consultant Medical Oncologist

National University Cancer Institute, Singapore

Targeting the Cancer Immunity Cycle

Chen and Mellman. Immunity 2013

Salgado et al Ann Oncol. 2014;26(2):259-271. doi:10.1093/annonc/mdu450

Goodman et al Mol Cancer Ther; 16(11) November 2017

ORRLow to intermediate TMB: 20%High TMB: 58% Multivariate p<0.001Median PFS: Low to intermediate TMB: 3.3mthsHigh TMB: 12.8 mthsMultivariate p<0.001Median OS:Low to intermediate TMB: 16.3 mthsHigh TMB: Not reachedMultivariate p=0.036

Tumour mutational burden in Gynaecological Cancers

Zehir et al Nature Medicine 2017

Ovarian ca subtype specific TMB: some hot some not?Chalmers et al. Genome Medicine (2017) 9:34: Analysis of 100,000 human cancer genomes

Immunotherapy in Breast Cancer

Lymphocyte predominant breast ca

Intra-epithelial TILs

(~10%)

Stromal TILs (sTILs)~80%

Modified from Adams et al JCO 2014

Primary TNBC

sTILs in breast ca subtypes

sTILs and outcomes in adj breast ca

trials

Loi et al Nature Reviews Cancer

2016

sTILs are prognostic and predictive of neoadjuvant

chemoresponse

Vanderbilt MD Anderson Institut de Cancérologie

Pathway analysis overlap:

Subset of TNBC across all profiles - altered immune checkpoint gene regulation

Le Du F Oncotarget. 2015

Molecular Subtypes of TNBC

TNBC ER positive

Mutation rate higher in TNBC compared to other subtypes

Luminal ALuminal BHER2BasalNormal

SynonymousNonsynonymous

10

8

6

4

0

2

No

. mu

tati

on

s/M

bSomatic mutations in breast cancer subtypes

Tumour mutation burden in breast cancers

Banerji S, et al. Nature. 2012;486(7403):405-409.

TNBC is most immunogenic breast ca

Salgado et al Ann Oncol. 2014;26(2):259-271

Pembrolizumab(n = 32)

Atezolizumab (n = 71)

Avelumab(n=58 /9)

Target PD-1 PD-L1 PD-L1

Tumour PD-L1 ≥1% (58%+) ≥5% All / ≥1%

ORR 18.5% 13% 8.6% / 44.4%

SD 25.9% 18% 22.4%

Immune Checkpoint inhibitors in Metastatic TNBC

Nanda et al. JCO 2016, Schmid et al. AACR 2017, Dirix et al SABCS 2015

Immune checkpoint inhibitors have shown durable responses in heavily pretreated patients with metastatic TNBC

Pembrolizumab in TNBC (n=32)PD-L1+ tumours: PD-L1 expression on tumour cells (>1%) (58% PD-L1+)

Nanda et al. SABCS 2014

Keynote-012: Pembrolizumab in TNBC Best Response

100

80

60

40

20

0

-20

-40

-60

-80

-100

Ch

ange

fro

m b

asel

ine

in s

um

of

lon

gest

dia

met

er o

f ta

rget

lesi

on

(%

)

Confirmed complete response (nodal disease)Confirmed partial responseStable diseaseProgressive disease

Objective response rate: 18.5%Stable disease: 25.9%Median DOR: not reached3 of 5 responding for more than 11mths

Schmid P, et al. AACR 2017

Atezolizumab in TNBC

Criteria MedianDOR

(range)

Median PFS

(95% CI)

RECIST v1.1

21.1 mo(2.8 to 26.5+)

1.4 mo(1.3, 1.6)

irRC 21.1 mo(2.8 to 33.9+)

1.9 mo(1.4, 2.6)

Overall TNBC cohort

Patients With RECIST v1.1 Response or Stable Disease

or irRC Response

irPRa

irPRairPR

irPR

Usual median OS in this population ~ 12 months.

Study KEYNOTE-086 Cohort A, Adams, S. et al. ASCO 2017

Patients

• Age ≥18 y

• Centrally confirmed TNBCa

• ≥1 prior systemic

treatment for mTNBC with

documented PD

• ECOG PS 0-1

• LDH <2.5 x ULN

• Tumor biopsy sample for

PD-L1 evaluation

• No radiographic evidence

of CNS metastases

• Measurable disease per

RECIST v1.1 by central

review

Pembrolizumab

200 mg IV Q3W

for 2 years or until PD,

intolerable toxicity,

patient withdrawal, or

investigator decision

• Primary end points: ORRb and safety• Secondary end pointsb: DOR, DCR,c PFS, OS

N = 170

Protocol-specified

follow-up

Best Overall Response (RECIST v1.1, Central Review)

Total

Populationa

N = 170

PD-L1 Positive

n = 105

PD-L1 Negative

n = 64

ORR, n (%) [95% CI] 8 (4.7) [2.3-9.2] 5 (4.8) [1.8-10.9] 3 (4.7) [1.1-13.4]

DCR,b n (%) [95% CI] 13 (7.6) [4.4-

12.7]

10 (9.5) [5.1-

16.8]

3 (4.7) [1.1-13.4]

Best Overall Response, n

(%)

Complete response 1 (0.6) 1 (1.0) 0

Partial response 7 (4.1) 4 (3.8) 3 (4.7)

Stable disease 35 (20.6) 22 (21.0) 12 (18.8)

Progressive disease 103 (60.6) 66 (62.9) 37 (57.8)

Not evaluablec 5 (2.9) 2 (1.9) 3 (4.7)

Not able to be assessedd 19 (11.2) 10 (9.5) 9 (14.1)

0 2 4 6 8 1 0 1 2 1 4 1 6

0

1 0

2 0

3 0

4 0

5 0

6 0

7 0

8 0

9 0

1 0 0

T im e , m o n th s

OS

, %

N o . a t r is k

8 8 8 8 8 4 0 0

35 35 35 33 29 16 1 0

1 0 3 94 72 63 39 20 1 0

9

2

7

4

Overall Survival by Best Overall Response

100%100%64.6%

100%89.6%39.0%

Events/P

ts, n

Median

(95% CI)

CR or

PR0/8

Not reached

(NR-NR)

SD 6/35Not reached

(12.7-NR)

PD 66/1037.1 mo

(6.3-8.8)

Exploratory Analysis

KEYNOTE-086 Cohort B: Study DesignAdams S et al. ASCO 2017

Patients• Age ≥18 years• Centrally confirmed mTNBCa

• No prior systemic therapy for metastatic disease

• ECOG PS 0-1• LDH <2.5 x ULN• PD-L1 CPS ≥1%• No radiographic evidence of

CNS metastases• Measurable disease per

RECIST v1.1 by central review

Pembrolizumab 200 mg IV Q3W

for 2 years or until PD, intolerable toxicity, patient withdrawal, or investigator

decision

N = 84Protocol-specified follow-up

• Primary end points: safety• Secondary end points: ORR, DCR,b DOR, PFS, OS

Pembrolizumab Antitumor Activity in Previously Treated and Previously Untreated mTNBC

Cohort A (N = 170): Previously Treated,

Regardless of PD-L1 Expression

Cohort B (N = 52)1: Previously Untreated,

PD-L1 Positive

0

4

8

12

16

20

24

28

32

36

40

OR

R, %

0

4

8

12

16

20

24

28

32

36

40

OR

R, %

23.1%

Complete response

Partial response

Total PD-L1Positive

PD-L1Negative

Total(All PD-L1 Positive)

Stable disease≥24 wk

4.7%

9.5%7.6%

KEYNOTE-086: sTIL Level and Tumor Response in mTNBC

Loi S, et al. ESMO 2017. Abstract LBA13.

Median sTIL, % (IQR) P Value

Combined cohorts▪ Responder (n = 18)▪ Nonresponder (n = 175)

37.5 (8.75-66.25)5 (2-15)

< .001

Cohort A▪ Responder (n = 7)▪ Nonresponder (n = 140)

10 (5-30)5 (1-10)

.062

Cohort B▪ Responder (n = 11)▪ Nonresponder (n = 35)

50 (35-70)15 (5-40)

.009

▪ sTIL level, cohort, and LDH level were independent predictors of tumor response to pembrolizumab

Pembrolizumab Antitumor Activity in Previously Treated and Previously Untreated mTNBC

Cohort A (N = 170): Previously Treated,

Regardless of PD-L1 Expression

Cohort B (N = 52)1: Previously Untreated,

PD-L1 Positive

0

4

8

12

16

20

24

28

32

36

40

OR

R, %

0

4

8

12

16

20

24

28

32

36

40

OR

R, %

23.1%

Complete response

Partial response

Total PD-L1Positive

PD-L1Negative

Total(All PD-L1 Positive)

Stable disease≥24 wk

4.7%

9.5%7.6%

Do immune check point

inhibitors work better earlier in

the course of disease?

Phase III, Randomized, Double-blind Study to Evaluate Pembrolizumab plusChemotherapy vs Placebo plus Chemotherapy as Neoadjuvant Therapy and Pembrolizumab vs Placebo as Adjuvant Therapy for TNBC (KEYNOTE-522)

TNBCT2 or N+

ER/PR < 1%N=855

2Surgery

Surgery

Primary end pointspCR and EFS

Secondary end point OS

carboplatin (AUC5 q3w or AUC1.5 qw) x 4 cycles

Stratification factors: Nodal status ,Tumor size, Choice of Carboplatin dose/schedule

1

Pembro 200 mg q3w

Placebo q3w

AC/EC x 4Pembro 200 mg

q3w X 9 cycles

carboplatin (AUC5 q3w or AUC1.5 qw) x 4 cycles

AC/EC x 4Placebo q3w X

9 cycles

wPaclitaxel x 4 cycles

wPaclitaxel x 4 cycles

Neoadjuvant Therapy in TRIPle Negative Breast Cancer With antiPDL1 (NeoTRIPaPDL1)

Surgery

Primary Endpoint

5 year Event Free Survival

Secondary Endpoints

pCR

Clinical Objective Response

Distant Event Free Survival

Safety and tolerability

AC/EC/FEC

x 4 cycles

TNBCER/PR < 1%

Stage III N=272

Randomized phase III

Carboplatin (AUC 2 D1,8 q3w)

q3w x 8 cycles

Atezolizumab 1200 mg q3w

x 8 cycles

nab-paclitaxel 125 mg/m2 D1, 8

q3w x 8 cycles

Carboplatin (AUC 2 D1,8 q3w)

q3w x 8 cycles

nab-paclitaxel 125 mg/m2 D1, 8

q3w x 8 cycles

Combination Immune-and Chemotherapy in TNBC

Nab-Paclitaxel + anti-PD-L1 (atezolizumab)

Adams S, SABCS 2015; Tolaney, S SABCS 2016, ESMO 2017

2nd/≥3rd line Patients

1st line Patients

All1st line (n=17)

2nd/3rd L (n=18)

ORR 34.4% 41.2% 27.3%

CBR 40.6% 47.1% 36.4%

Eribulin + anti-PD-1 (pembrolizumab)

Independent of PD-L1 status

IMpassion130: Atezolizumab in 1st line mTNBC

Central testing forPD-L1 status

Patients with incurable advanced/

metastatic TNBC (N=900)

R1:1

Surv

ival

Fo

llow

-Up

Study treatment phase

Un

til P

D

Stratification: • Tumour tissue PD-L1 expression

(IHC 0 vs IHC 1,2,3)• Liver metastases (Yes vs No)• Prior taxane treatment (Yes vs No)

Un

til l

oss

of

Clin

ical

Ben

efit

Placebo + nab-paclitaxel (100mg/m2 qw)

Atezolizumab (840mg q2w) + nab-paclitaxel (100mg/m2 qw)

KN-355: Randomized Phase III of Pembrolizumab + Chemo

vs Placebo + Chemo in 1st line mTNBC

#Treatment may be continued

until confirmation of PD

N=828

▪Previously untreated locally recurrent inoperable or metastatic TNBC▪Central determination of TNBC and PD-L1 ▪No active CNS metastases

Pembrolizumab + Chemotherapy*

Placebo**

+ Chemotherapy*

Protocol-Specified

Follow-Up

Progressive Disease#/Cessation of Study

Therapy2:1

*Paclitaxel, nab-paclitaxel or

gemcitabine/carboplatin**Normal saline

Primary Endpts➢ PFS in all subjects

and PD-L1-positive

➢ OS in all subjects and PD-L1-positive

2nd Endpoints➢ ORR, DCR, DOR in

all subjects and PD-L1-positive

➢ Safety

Summary of IO studies in breast caTNBC

ER+ve

Loi et al NRC 2016

Summary of status of breast cancer immunotherapy investigational trials, by phase.

Robert H. Vonderheide et al. Clin Cancer Res

2017;23:2640-2646

Natural Killer Cell Therapy - HER2 Basket Study

Trastuzumab + Natural Killer cell therapy for all HER2 amplified/ IHC 3+ tumours Currently recruiting

Dario Campana Lee Soo Chin

Immunotherapy for Ovarian Cancer

Potential Cellular Origins of Ovarian Cancer Subtypes

Prat J Ann Oncol 2012

Ovarian Cancer: Different subtypes = Different Origins = Different Molecular

Abnormalities

Role of Immune Cells in Ovarian Cancer

• OC is an immunogenic

tumour1-4

– Strong immunosuppressive

environment present in OC

– Spontaneous antitumor immune

response can be detected in the

form of tumor-reactive T cells

and antibodies

• Analyses of OC patient

samples showed presence of

intratumoral T cells was

associated with better clinical

outcome4

1. Turner TB et al. Gynecol Oncol. 2016;142:349-356. 2. Coukos G et al. Ann Oncol. 2016;27(suppl 1):i11-i15. 3.

Mandai M et al. Int J Clin Oncol. 2016;21:456-461. 4. Zhang L et al. N Engl J Med. 2003;348:203–213.

Ove

rall

Su

rviv

al

(%)

Month

0

25

50

75

100

0 12 24 36 48 60 72 84 96 108 120 132

P<0.001

Intratumoral T cells

No intratumoral T cells

Classification of tumours based on TILs and PDL1 expression

Teng et al Cancer Res; 75(11) June 1, 2015

EOC Histotype and Tumour MicroenvironmentWebber et al Gynecol Onc 2016

Taube et al 2014Smyth et al 2016

Heong et al J Gynecol Oncol. 2017

Immune Checkpoint Inhibitors in Ovarian Cancer

Responses in unselected EOC only ~10-15%

Avelumab (PD-L1 inhibitor) in EOC: Response by subgroup

Unconfirmed ORR by RECIST 1.1

n (%) 95% CI

Tumor burden (median sum of longest diameter=58 mm)

> median (n=35) 2 (5.7%) (0.7, 19.2)

≤ median (n=40) 6 (15.0%) (5.7, 29.8)

# of prior treatment lines for locally advanced or metastatic disease, excluding adjuvant therapy

≥3 (n=51) 4 (7.8%) (2.2, 18.9)

2 (n=10) 1 (10.0%) (2.5, 44.5)

≤1 (n=14) 3 (21.4%) (4.7, 50.8)

Platinum resistance/sensitivity*

Resistant (<6 month PFI; n=44) 4 (9.1%) (2.5, 21.7)

6-12 month PFI (n=18) 2 (11.1%) (1.4, 34.7)

Sensitive (>12 month PFI; n=10) 2 (20.0%) (2.5, 55.6)

* Defined based on platinum-free interval (PFI) since last line of platinum:<6 months, 6-12 months, and > 12 months; PFI could not be determined for 3 patientsDisis et al ASCO 2015

Earlier use in platinum sensitive disease better?

First Line Avelumab + Chemo: JAVELIN 100

B9991010

Observation

Avelumab Q2W

Chemotherapy

Chemotherapy

Chemotherapy Maintenance

Chemotherapy + Avelumab Q3W

Avelumab Q2W

RANDOMIZATION

Arm A

Arm B

Arm C

Eligibility Criteria• Previously untreated• Stage III-IV• Prior debulking surgery or plan for neoadjuvant chemotherapy • ECOG PS 0 or 1• Mandatory archival tissue

Chemotherapy: Choice of carboplatin + q3w, paclitaxel, OR carboplatin + weekly paclitaxelMaintenance avelumab up to 24 months

n = ~951 (388 PFS events) 272 events within each of the 2 main comparisons

Primary endpoint:

PFS from randomization (A vs B, A vs C)

Secondary endpoints:

Maintenance PFS, OS, ORR, duration of response, pCR, PFS2, PROs, safety, PK

Patients whose tumor was not progressing as per RECIST 1.1 criteria (CR, PR, or SD) will be allowed to continue onto the maintenance portion of the study

ClinicalTrials.gov Identifier:NCT02718417

First Line Atezolizumab and bevacizumab

IMaGYN050 Study Design: Primary Surgery Cohort

Stratification variables:• Stage/debulking status• GOG PS• PDL1 IC 0 vs IC1+• Adjuvant/Neo-adjuvant

Paclitaxel 175 mg/m2 Q3wk

Carboplatin AUC 6 Q3wk

Carboplatin AUC 6 Q3wk

Paclitaxel 175 mg/m2 Q3wk

R

1:1

• Previously untreated epithelial ovarian, primary peritoneal, or fallopian tube cancer

• Stage III (sub-optimal/ optimal w/ macroscopic residual), Stage IV, or patients w/ advanced disease treated in the neo-adjuvant setting

• GOG PS 0-2

PL q3w X 22 cycles

Atezo 1200mg q3w x 22cycles

No cross-over

Co-Primary endpoint: PFS &OS in all comers and Dx+ (IC 1+)

Bev 15 mg/kg Q3wk

Bev 15 mg/kg Q3wk

Bev 15 mg/kg X 16 cycles

Bev 15 mg/kg X 16 cycles

Double blinded, 1:1 randomized, placebo-controlled multi-center study

ClinicalTrials.gov Identifier: NCT03038100

Platinum sensitive recurrent EOC

Platinum resistant disease: Phase 3

Combination IO + PARP inhibitor / VEGFR inhibitor

IO agent Disease status Phase N Result G3/4 Adverse events

Durvalumab + olaparib

Recurrent EOC I/II 10 PR (1;11+mths)SD (7;4+mths)

Lymphopenia,anemia

Durvalumab + cediranib

Recurrent EOC I/II 4 PR (1;7mths)SD (2;1 for 6mths)

Lymphopenia, anemia, nausea,

pulmonary hypertension,

PE, hypertension,

fatigue, headache

Lee J, J Clin Oncol. 2016:34(suppl; abstr 3015)

Ongoing studies of Immune

checkpoint inhibitors in

ovarian cancer

Gaillard et al. Gynecologic Oncology Research and Practice (2016) 3:11

But many questions….

• How to select EOC patients?

– single vs combo?

• Biomarkers?

• Optimal combinations?

• Timing of treatment?

– First line/ plat sens recurrence/ plat resistant disease?

Will ongoing studies answer these questions???

Epi-AMesStem-AStem-B

Epi-B

Mesenchymal

IFN-inducibleMHC Class IIIgs

Stem-A

Epi-A/Stem

Epithelial

VCAM1

ZEB1

FN1

PDGFRA

TWIST1

OAS1/2

HLA-Ds

IGH/K/Ls

MYCN

CDH3/2

NCAM1

TOP2A/BUB1/CCNE1/CENPA

LGR5

WNT5A

DKK3

SFRP1

PROM1

XIST

KRT6A/17/14/19/7

EPCAM

CD24

CDH1

MUC1

Epi-A

Epi-B

Mes

Stem-A

Stem-B

p < 0.0001

Molecular subgroups of EOC e.g. Epithelial/ C2/ Immunoreactive,

Mesenchymal/C1 , or Stem-like/ C5/ Proliferative with distinct survival

outcomes.

Are EOC Gene expression molecular subtypes helpful?

Tan, Miow & Huang et al., EMBO Mol Med, 2013

❖ Meta-analysis (Tan, Miow, &

Huang et al., EMBO MM, 2013) of

1,538 EOCs including all

histological types.

4 subtypes showing survival

differences

Molecular subtypes likely to reflect aggregate phenotype of tumour cells & microenvironmental factors

Balkwill et al Journal of Cell Science, 2012

Outcome of ‘immune’ and ‘proangiogenic’

groups of ovarian cancer in ICON 7

Bev had adverse

effect on PFS in

immune

subgroup

Benefit in pro-

angiogenic

subgroup

Control arm

ICON7

Immune and

proangiogenic

groups

Gourley et al ASCO 2014

EpiB/ C2 (immunoreactive) subtype for immunotherapy?

C2 = immuno-reactive mol. subtype

EpiB / C2 (immunogenic) subtype: The Shirley Pepke Story

3/3 responses to PD1/PDL1 inhibitor in ovarian clear cell cancer(OCCC)

Disis et ASCO 2015 Hamanishi et al JC 2015

Baseline: 69 mm RLL lesion Week 25: 41 mm (-40.6%)

Are PDL1/PD1 inhibitors more likely to work in OCCCs?

Avelumab2/2 OCCC responses

Nivolumab1/1 OCCC response -CR

The Emerging Molecular Landscape of OCCCs

Tan et al BJC 2013

Upregulation of IL6 in OCCC: a marker of tumour inflammation

IL-6

Anglesio et al CCR 2011

Huang CCR 2007

High IL-6(H score ≥150)

PD-L1 +ve(PD-L1 ≥ 1%)

PD-L1 –ve(PD-L1 < 1%)

Low IL-6(H score < 150)

OCCC IL6 and PD-L1 expression, n=103: Courtesy of Dr D. Lim

86% 14%

17% 83%Diana Lim et al (unpublished)

Chandler et al Nature Comm 2015

ARID1A and PIK3CA mutations cooperate to promote tumour growth

through sustained IL-6 overproduction.

0 5 0 1 0 0 1 5 0

0

5 0

1 0 0

M o n t h

Pe

rc

en

t s

ur

viv

al

ClinicaloutcomesbasedonOCCCirGESsubtypes

P=0.0864

OverallSurvival(n=74)

Overallsurvival(%

)

Recurrence-FreeSurvival(n=74)

0 5 0 1 0 0 1 5 0

0

5 0

1 0 0

M o n t h

Pe

rc

en

t s

ur

viv

al

Recurrencefreesurvival(%

)

G1

G2

G3

G4

G1

G2

G3

G4

P=0.0284

Months

Months

OCCC gene expression subtypes

Heong et al ESMO 2017

74 OCCCs using nanoString nCounterPanCancer Immune Profiling Panel

G1 (NK cell and PD-1

enriched) and

G2 (CTLA-4 high)

subgroups of OCCC

associated with

worse outcomes

Clinical Responses

to PD-1 inhibitor

pembrolizumab in

MMR deficient vsproficient cancers

Le DT et al. N Engl J Med 2015;372:2509-2520

Best response to pembrolizumab in MSI-H non-colorectal tumours

Diaz et al ASCO 2016

• Ovarian cancers developed at mean 48 years of age

• FIGO stage I in 47% of cases

• Histologically, endometrioid (35%) and clear cell (17%) tumors were overrepresented.

• The underlying MMR gene mutations in these families affected MSH2 in 49%, MSH6 in 33% and MLH1 in 17%.

• IHC loss of the corresponding MMR protein in 92% of tumors

Gynecologic Oncology 121 (2011) 462–465

OCCC: a genetically inherited disease?

A Multicentre Phase II randomised trial of MEDI4736 (DURVALUMAB) versus physician’s choice chemotherapy in

recurrent ovarian clear cell adenocarcinomas (MOCCA)

Relapsed Clear Cell

Cancer Ovarian Cancer

(>70% clear cell)

Inclusion

-Histologically confirmed

- WT1 negative

-Relapsed after at least 1

line of platinum-based

chemotherapy

-Measurable disease by

RECIST 1.1

-ECOG 0 / 1

Exclusion

-Concurrent use of

experimental anti-cancer

agent

-Untreated brain mets

MEDI-4736

(Durvalumab)

1500mg 4 weekly

for max. 24mths

CAELYX or

Investigator’s choice if

prior Rx included caelyx

(but antiangiogenic

therapy not permitted)

Crossover

on PD

2:1

randomisation

2

1

Singapore (GOGS)

Korea (KGOG)

Australia (ANZGOG)

N = 31

N = 15

Endpoint: PFS

What’s next for Immunotherapy in Gynae Cancer

Cold to hot immunologic conversion

Robert H. Vonderheide et al. Clin Cancer Res

2017;23:2640-2646

Immunotherapy combinations

Heong et al J Gynecol Oncol. 2017 Mar;28(2):e20.

Phase I study of Combined Medi4736 (Durvalumab, PD-L1 inhibitor), PARP inhibitor (Olaparib), and AKT inhibitor

(AZD5363) in Solid Tumours (MediPAC Study)

Funded by NMRC IAF GrantPI: David Tan

All comer Solid

Tumours

Recruiting from 1st quarter 2018

Journal of Thoracic Oncology, 2017 Vol. 12 No. 5

Can the gut microbiome boost immunotherapy?

Snyder et al Science 2015Science, 27 NOVEMBER 2015 • VOL 350 ISSUE 6264

Summary: Immunotherapy in Breast & Ovarian Cancers

• Specific subtypes are immunogenic – TNBC, OCCC, MSI-H/ MSI

• Immune checkpoint inhibitors effective as single agent is small proportion of unselected patients ~10-15%

• Combination strategies being explored

• Additional immunotherapy modalities e.g. adoptive cellular therapy, being explored

• Biomarkers crucial e.g.?cancer immunogram, ?gut microbiota, ?gene expression– Guide optimal combination of immunotherapy modalities

– Guide timing and selection of agents in patients

david_sp_tan@nuhs.edu.sg

THANK YOU

Acknowledgements:Rebecca Dent (My breast friend)National Cancer Centre, Singapore