Check point inhibitors for NSCLC: How does it work ... · Check point inhibitors for NSCLC: How does it work ... • History of nodular sclerosing Hodgkin ... WE could change this

Check point inhibitors for NSCLC:How does it work & available data

Solange Peters, MD-PhDOncology Department & Ludwig InstitueCHUV LausanneSwitzerland

Anti-PDL1 activity in metastatic NSCLC

• 55 year old white male• ECOG PS 0• Adenocarcinoma, without EGFR, BRAF, HER 2, KRAS, NRAS,

PIK3CA mutation, neither ALK translocation; T3N2M1b(mediastinal lymph nodes, bone and retroperitoneal mets)diagnosed in october 2012.

• Pulmonary, adrenal, subcutaneous and nodal progression injune 2014 after 4 lines of systemic therapy (carbo/pemetrexed& maintenance, carbo/gemzar, carbo/vinorelbine) anderlotinib.

• History of nodular sclerosing Hodgkin Lymphoma indocumented complete remission since 2001.

Baseline CT scan

June 2014

3 months after beginning

October 2014

Pulmonary, adrenal and peritoneal progression 7 months after beginning

February 2015

March 2015: onset of pulmonary and adrenal radiotherapy and ongoinganti-PDL1Not completed by PS 3, anemia and pulmonary embolism. Death 07/15

Stable disease from october 2014 to january 2015, working, PS 1

“In any trial you getthe odd patient whodoes very well, butthis is an order ofmagnitude abovethat.”, Mick Peake,Glenfield Hospital

Vogelstein, Science 2013

Melanomas and lung tumorsdisplay many more mutations thanaverage, with~200 nonsynonymousmutations per tumor.

These larger numbers reflect theinvolvement of potent mutagens.Accordingly, lung cancers fromsmokers have 10 times as manysomatic mutations as those fromnonsmokers.

Hanahan & Weinberg. Cell 2011

Evadinggrowth

suppressors

Enablingreplicativeimmortality

Tumour-promoting

inflammation

Activatinginvasion &metastasis

Genomeinstabilitymutation

Resistingcell

death

Degradingcellular

energetics

Sustainingproliferativesignalling

Inducingangiogenesis

PD-1

PDL-1

Avoidingimmune

destruction

Therapeutic Intervention atCancer Hallmarks

CTLA-4

PD-1

Tumor CellTumor Cell MHC

CD8+CD8+

TCR

STATSTAT

INF-γ

Tumor

Immune Checkpoint Receptor: CTLA-4 & PD-1

Lymphnode

CTLA-4

B7

DendriticCell

DendriticCell

CD8+CD8+

TCR

MHC

Priming phase Effector phase

Ipilimimab Phase 2 CA184-041:Study Schema

Lynch et al, JCO 2012

Lung cancer immunomodulationIpilimumab

irPFS OS

Lynch et al, JCO 2012

Ipilimumab: NSCLC phase III trial

Squamous Cell NSCLC, stage IV. Primary EP: OS

N=920, accrual completed

PD-1 axis immunotherapy for NSCLC

1) A new generation of expanded phase 1/2 trials for activityevaluation

2) Evidence-based data for checkpoint inhibitors monotherapy

3) Current evidence for biomarker-based selection of NSCLCpatients

• Tumour mutation load• PD-L1 expression• Tumour infiltrating lymphocytes• Tumour molecular characteristics

4) Upfront perspectives for checkpoint inhibitors







Clinical Development of Inhibitors ofPD-1 Immune Checkpoint

PD-1 NivolumabBMS-936558

Fully human IgG4 mAb Bristol-Myers Squibb Phase III

PidilizumabCT-011

Humanized IgG1 mAb CureTech Phase II

PembrolizumabMK-3475

Humanized IgG4 mAb Merck Phase III

AMP-224 Recombinant PD-L2-Fcfusion protein

GlaxoSmithKline Phase I

PD-L1 BMS-936559 Fully human IgG4 mAb Bristol-Myers Squibb Phase II

DurvalumabMedI-4736

Engineered human IgG1mAb

MedImmune Phase III

AtezolizumabMPDL-3280A


Genentech Phase III

AvelumabMSB0010718C


EMD Serono Phase III

OS in Nivolumab phase 1 (3yrs FU)

• Pts were heavily pretreated; 54% had 3–5 prior therapies

Gettinger, JCO 2015

Pembrolizumab phase 1 data

Pretreated pts. Same efficacy 2mg or 10mg/kgSoria, ESMO 2015

Pembrolizumab phase 1 data

Hellmann, WCLC 2015

Pembrolizumab long-term phase 1 FU

Soria, ESMO 2015FU 16 months

Atezolizumab : PD-L1 Expression on TCand IC as a potential predictive

biomarker

Vansteenkiste & Schmid ESMO 2015

Atezolizumab : biomarker in phase 2BIRCH trial

Besse, ESMO 2015

Besse B, et al, atezolizumab in NSCLC (BIRCH)

BIRCH: Objective Response RateTC3 or IC3 Subgroup vs TC2/3 or IC2/3 Subgroup by Cohort

0

10

20

30

1L 2L 3L+

26%24%

27%

19%17% 17%

8

BIRCH met its primary endpoint in all predefined subgroups per protocol specified criteria

Enriched clinical benefit was observed in TC3 or IC3 patients

ORR data were similar using RECIST V1.1 or mRECIST criteria

Responses were observed in patients with EGFR or KRAS mutations, although patientnumbers were small

TC2/3 or IC2/3

TC3 or IC3

OR

R,%

N=115 N=253N=267N=139N=65 N=122


Progression-free Survival by IRF per RECIST v1.1

Line ofTherapy PD-L1 Status

Median PFS(95% CI), mo

6-month PFSRate

3L+ TC3 or IC3 4.2 (2.8, 5.6) 39%

3L+ TC2/3 or IC2/3 2.8 (2.7, 3.7) 31%

2L TC3 or IC3 4.1 (1.8, 5.5) 34%

2L TC2/3 or IC2/3 2.8 (1.5, 3.5) 29%

1L TC3 or IC3 5.5 (2.7, 8.3) 48%

1L TC2/3 or IC2/3 5.5 (3.0, 6.9) 46%

12Data cut-off May 28, 2015.


BIRCH: Overall Survival by CohortTC2/3 or IC2/3 Subgroup

Data cut-off May 28, 2015.

Subgroup Median OS, mo(95% CI)

6-moOS, %

Cohort 1 (1L) 14.0 (14.0, NE) 82%

Cohort 2 (2L) NE (11.2, NE) 76%

Cohort 3 (3L+) NE (8.4, NE) 71%

27


BIRCH: Overall Survival by CohortTC3 or IC3 Subgroup

28Data cut-off May 28, 2015. 11

Subgroup Median OS,mo (95% CI)

6-mo OS, %

Cohort 1 (1L) NE (10.4, NE) 79%

Cohort 2 (2L) NE (10.6, NE) 80%

Cohort 3 (3L+) NE (NE, NE) 75%

A similar and significant tail of thecurve across trials

A similar and significant tail of thecurve across trials

Soria, ESMO 2015FU 16 months

Activity in pretreated patientsNivolumab Pembrolizuma

bAtezolizuma

bDurvalumab Avelumab

N 129 4751 175 228 184

RRSquamous

Non Sq.17%18%

23.5%19%

27%21%

21%13%

14%

Drug relAE

All gradesGrade 3/4

41%4.7%

71%9.5%

66%11%

50%8%

77%12%

RRPDL-1 +PDL-1 -

16%13%

42% (>50%)10% (<1%)

34% IC2/3 orTC 2/3 (half

if 3 used)

Gettinger S, J Clin Oncol 2015; 33: 2004-2012; Herbst R, Nature 2014; 515: 563-7; Soria JC, ESMO 2013;Garon E, NEJM 2015; 372: 2018-28; Rizvi N, ASCO 2015; Guley LJ, ASCO 2015

Proportion of high expressors?

Agent Atezolizumab1 Pembrolizumab Nivolumab3,4

Highest PD-L1+cut-off

TC3 or IC3 TC ≥50% TC ≥10%

Trial/Analysis

MDACC andUCCC tumorspecimens1

POPLAR2 KEYNOTE-0013 CheckMate0574

CheckMate0175

Total samples 698 287 91 582 272

Positivebased oncut-off

26% 16% 29.7% 12.4% 25.4%

MDACC=MD Anderson Cancer Center; UCCC=University of Colorado Cancer Center.1. Gettinger SN, et al. Presented at: ASCO; May 29-June 2, 2015, Abstract 3015. 2. Spira A, et al. Presented at: ASCO; May 29-June 2, 2015, Abstract8010. 3. Rizvi N et al. Presented at ASCO; May 29-June 2, 2015, Abstract 8026. 4. Paz-Ares L,, et al. Presented at: ASCO; May 30-June 3, 2014;Chicago, Illinois. Abstract LBA 109. 5. Brahmer J, et al. N Engl J Med. 2015 May 31. [Epub ahead of print].







Second line single agentchemotherapy improves survival

The database for a survival advantage of 2nd line chemotherapy issmall and based on only one study of docetaxel vs BSC

Shepherd, J Clin Oncol 2000

Poplar: atezolizumab vs docetaxelRandomized phase 2

Vansteenkiste, ESMO 2015





Both PD-L1 expression on TC and IC areindependent predictors of overall survival

Vansteenkiste & Schmid ESMO 2015

Primary Objective

• Overall survival (OS)

Secondary Objectives

• ORR

• PFS

• ORR and OS by PD-L1 status

• Duration of OR

• Time to OR

• Proportion of patients exhibiting disease-related symptom progression (Lung CancerSymptom Scale)

Docetaxel

Nivolumab

Docetaxel

Nivolumab

CA209-017NCT01642004

(Phase 3; N = 264)

Patients with stageIIIb/IV squamous

cell NSCLC

CA209-057NCT01673867

(Phase 3; N = 574)

Patientswith stage IIIb/IV

non-squamous cellNSCLC

Nivolumab phase III trialSquamous & non-squamous

2nd line vs docetaxel

Luis Paz Ares�

WE could change this slide by one describing phase III trials of MPDL3280A�

16th World Conference on Lung Cancer, September 6-9, 2015 ̶ Denver, CO, USA

Overall Survival

Based on August 2015 DBL.Symbols refer to censored observations.

Nivolumab

n=135

Docetaxeln=137

mOS mo(95% CI)

9.2(7.33,12.62)

6.0(5.29,7.39)

# events 103 122

HR=0.62 (0.48, 0.81); P=0.0004

Minimum follow-up for survival: 18 months• Survival was monitored until death or withdrawal of consent

Docetaxel

18-month OS rate=13%

OS

(%)

Time (months)

0614253751576986113135 0Nivolumab

Number of Patients at Risk

047111722334669104137Docetaxel 1

Nivolumab18-month OS rate=28%

100

90

80

70

60

50

40

30

10

0

20

332724211815129630 30

RR: 20% vs 9%

16th World Conference on Lung Cancer, September 6-9, 2015 ̶ Denver, CO, USA

Efficacy by PD-L1 Expression

Based on December 2014 DBL

18th ECCO ̶ 40th ESMO European Cancer Congress, September 25-29, 2015, Vienna, Austria Note: this draft is currently undergoing editorial review and QC

DRAFT: Highly Confidential

12-mo OSa 18-mo OSb

Nivo (n = 292) Doc (n = 290) Nivo (n = 292) Doc (n= 290)

mOS, mos 12.2 9.4 12.2 9.4

1-year OS rate, % 51 39 51 39

18-mo OS rate, % – – 39 23

No. of events, n/N 190/292 223/290 206/292 236/290

HR (96% CI) = 0.73 (0.59, 0.89)P = 0.0015

HR (95% CI) = 0.72 (0.60, 0.88)Post-hoc P = 0.0009c

aBased on a March 18, 2015; bBased on a July 2, 2015 DBL; cThe formal primary endpoint testing was based on the interim analysis (March 18, 2015). For full description of the additionalfollow-up data, an updated p-value is provided based on the July 2, 2015 DBLSymbols represent censored observations

Overall Survival

• Minimum follow-up for 12-mo OS rate, 13.2 mos; for 18-mo OS rate, 17.1 mos

100

90

80

70

60

50

40

30

10

0

20

27181596 211230 24 30

NivolumabDocetaxel

Number of patients at risk (18-mo OS)b

292 233 195 171 148 128 107 55 427

290 244 194 150 111 89 61 23 4

0

06

Nivolumab

Docetaxel

NivolumabDocetaxel

Number of patients at risk (12-mo OS)a

292 232 194 169 146 123 62 32 09

290 244 194 150 111 88 34 10 05

18-mo OS rate = 23%

18-mo OS rate = 39%

1-yr OS rate = 39%

1-yr OS rate = 51%

Time (Months)

OS

(%)

RR: 12% vs 9%

18th ECCO ̶ 40th ESMO European Cancer Congress, September 25-29, 2015, Vienna, Austria Note: this draft is currently undergoing editorial review and QC

DRAFT: Highly Confidential

OS by Baseline PD-L1 Expression

43

PD-L1expression level

Nivon

Docn

UnstratifiedHR (95% Cl)

InteractionP-valuea

OS

≥1% 123 123 0.59 (0.43, 0.82)0.0646

<1% 108 101 0.90 (0.66, 1.24)

≥5% 95 86 0.43 (0.30, 0.63)0.0004

<5% 136 138 1.01 (0.77, 1.34)

≥10% 86 79 0.40 (0.26, 0.59)0.0002

<10% 145 145 1.00 (0.76, 1.31)

Not quantifiable 61 66 0.91 (0.61, 1.35)

PFS

≥1% 123 123 0.70 (0.53, 0.94)0.0227

<1% 108 101 1.19 (0.88, 1.61)

≥5% 95 86 0.54 (0.39, 0.76)<0.0001

<5% 136 138 1.31 (1.01, 1.71)

≥10% 86 79 0.52 (0.37, 0.75)0.0002

<10% 145 145 1.24 (0.96, 1.61)

Not quantifiable 61 66 1.06 (0.73, 1.56)

Based on a March 18, 2015 DBLaInteraction p-value from Cox proportional hazard model with treatment, PD-L1expression and treatment by PD-L1 expression interaction

PD-L1 expressors

PD-L1 non-expressors

PD-L1 not quantifiable

1.00.5 2.00.25Nivo Doc

Clinical trial OS all OS non SQCC OS squamous

Docetaxel vsBSC

7 vs 4.6 NA NA

Docetaxel vsPem

7.9 vs 8.3 8 vs 9.3 7.4 vs 6.2

Docetaxel vsErlotinib

8.2 vs 5.4 NA NA (24%)

Docetaxelramucirumabvs Docetaxel

10.5 vs 9.1 11.1 vs 9.7 9.5 vs 8.2

Docetaxelnintendanib vsDocetaxel

10.1 vs 9.1 12.6 vs 10.3 8.6 vs 8.7

Nivolumab vsDocetaxel

NA 12.2 vs 9.4 9.2 vs 6.0

Atezolizumabvs Docetaxel

11.4 vs 9.5 NA NA

Docetaxel randomized results in 15 years

Lets discuss toxicty…

Toxicité Nivolumabsquamous %

Docetaxelsquamous %

Afatinibsquamous %

Docetaxel /Ramucirumab%

All 59 87 93 98

Grade 3-4 8 58 57 79

Grade 5 0 2 2 5

18th ECCO ̶ 40th ESMO European Cancer Congress, September 25-29, 2015, Vienna, Austria

Squamous : EQ-5D Utility IndexMean Scores Over Time While on Treatment

Lung Cancer Norm (UK-based): 0.67b

Me

an

EQ

-5D

Uti

lity

Ind

ex

Sc

ore

97 50 32 32 21 18 13 13 8Nivolumab (n = 97)

88 32 9 5 5 4 4 2 1Docetaxel (n = 89)

0 12 24 30 36 42 48 54 60

1.0

0.9

0.8

0.7

0.6

0.5

0.4

Population Norma

Docetaxel

Nivolumab

aBharmal M, Thomas J 3rd. Value Health. 2006;9:262–71.bPickard AS, et al. Health Qual Life Outcomes. 2007;5:70.46

Higher scores indicate better health status.Only time points that had PRO data available for ≥5 patients in either treatment arm are plotted on the graph.

Week

18th ECCO ̶ 40th ESMO European Cancer Congress, September 25-29, 2015, Vienna, Austria

100

90

80

70

60

50

40

30

20

10

0

EQ-5D VASMean Scores Over Time While on Treatment

Me

an

EQ

-5D

VA

SS

co

re

97 50 32 32 21 18 13 13 8Nivolumab (n = 97)

88 32 9 5 5 4 4 2 1Docetaxel (n = 89)

47

aBharmal M, Thomas J 3rd. Value Health. 2006;9:262–71.bPickard AS, et al. Health Qual Life Outcomes. 2007;5:70.

Higher scores indicate better health status.Only time points that had PRO data available for ≥5 patients in either treatment arm are plotted on the graph.

Lung Cancer Norm: 68b

Population Norm: 80.05a

Docetaxel

Nivolumab

0 12 24 30 36 42 48 54 60

Week






4) Upfront for checkpoint inhibitors

Mutation load counts, but is not realistic inour daily practice

Rizvi, Science 2015

Efficacy also correlates with the molecular smoking signaturecharacteristic of squamous carcinoma

Intricate role of PD-1 signalling withdifferent cell types

Image from J. Allison

PD-L1 positivity is a flexible concept

Limitations in defining PD-L1 as thebiomarker

•PD-L1 “biomarker” is to be defined (mAB, platform &technique, criteria & thresholds, tumour material & sampling)

•PD-L1 expression is dynamic

•PD-L1 is heterogeneous within tissue

•Cytoplasmic vs membranous?

•Quality of the biopsy

•Importance of co-localization with TILs

•We dont know how to handle a continuous variable as abiomarker and need a prospective validation!

What do we know aboutT-cells infiltration in NSCLC

Liu H et al. Cancer Immunol Immunother 2012

Presence of TILs associated withincreased recurrence-free survival1

Re

curr

en

ce-F

ree

Surv

ival

(%)

Survival Time (Months)24 3612 48 600

0.00.10.20.30.40.50.60.70.80.91.0

FoxP3+ cell <3

FoxP3+ cell ≥3Re

curr

en

ce-F

ree

Surv

ival

(%) 1.0

0.8

0.6

0.4

0.2

0.0

0.0 10 20 30 40 50 60Survival Time (Months)

TIL–

TIL+

P=0.011

Higher NSCLC-Infiltrating Tregs associated withworse recurrence-free survival2

1. Shimizu K, et al.

J Thorac Oncol. 2010

2. Horne ZD, et al.

J Surg Res. 2011

TILs must be further characterized. Tissue is a limiting factor!

High Tumor Teff gene signature Isassociated with improved

OS benefit with atezolizumab

Teff: CD8A, GZMA, GZMB, IGN-γ, EOMES, CXCL9, CXCL10, TBX21

Schmid, ECCO 2015

PD-L2/B7

• High expression of each componentof the PD-1/B7.1 is associated withimproved OS with atezolizumab.

• Blocking PD-1/PD-L1 signaling inhighly immunologicallydysfunctional tumors my be capableof reversing T-cell exhaustion andimproving clinical benefit.

Schmid, ECCO 2015

Checkpoint inhibitorsin « oncogene-addicted » NSCLC ?

MK-3475 NORRa

% (95% CI)

EGRFR mutation 36 14 (5-30)

ALK rearrangement 6 17 (0-64)

Gettinger, ASCO 2014Garon, ESMO 2014Horn, WLCC 2013

The real-life study…

ALK treated patients represent a very small subset today.However, ALK protein might represent an interesting neo-antigen.

Need to induce T-cell response•Combinations with otherimmunotherapy strategies:checkpoints modulators/ TLRagonists / oncolytic viruses/cytokines / vaccines/targeted therapies• What about chemotherapy?

Do we expect a potentialrole for immunotherapy in

this patient population?

Functional MHC class 1 presentation ANDProbably (but not exclusively):-PD-L1 positivity AND/OR-Specific TILs tumour infiltration AND/OR-High mutation load (smoking, mismatchrepair…) AND/OR-Expression of potent neo-antigens AND/OR-Others: interferon signature, …?

Are we confident inaccurately identifying

these patients?

PD-L1 as a biomarker

0

2

4

6

8

10

12

0 10 20 30 40 50 60 70 80 90 100

PD-L1 IHC score

‘Negative’ ‘Positive’

Response?

Differentialeffectsdepend upon theDose-responserelationship

Are we ready to select patients ?

Schreiber, Science. 2011

Complexity of immune surveillance and escape mightprevent us from identifying a simple & unique predictivebiomarker.


1) A new generation of expanded phase 1 trials for activityevaluation





CI, confidence interval; HR, hazard ratioScagliotti GV, et al. J Clin Oncol. 2008;26(21):3543-3551.

Pemetrexed vs Gemcitabine (+CDDP)

• Adenocarcinoma

→ Pemetrexedbetter

OS: 11.8

PFS: 5.3

• SCC

→ Gemcitabinebetter

OS: 10.8

PFS : 5.5

RR : 31% pem vs 29% gem

Bevacizumab in Nonsquamous NSCLC:Key Results

E45991 AVAiL2,3 JO199074

OutcomePAC-CP-

BEVPAC-CP CP-GEM (7.5)

CP-GEM(15)

PACPAC-CP-BEV

PAC-CP

ORR, % 35 15 34.1 30.4 20.1 60.7 31.0

P<.001 P<.0001 P = .0002 .001

HR for PFS0.66

(P<.001)0.75

(P = .003)0.82

(P = .03)0.61

(P = .009)

Median PFS,months

6.2 4.5 6.7 6.5 6.1 6.9 5.9

HR for OS 0.79 (P = .003)0.93(NS)

1.03(NS)

0.99(P = .95)

Median OS,months

12.3 10.3 13.6 13.4 13.1 22.8 23.4

OS, overall survival; PFS, progression-free survival

1. Sandler A, et al. N Engl J Med. 2006;355(24):2542-2550. 2. Reck M, et al. J Clin Oncol. 2009;27(8):1227-1234.3. Reck M, et al. Ann Oncol. 2010;21(9):1804-1809. 4. Ichinose Y, et al. Eur J Cancer Suppl. 2009;7(2): Abstract O-9008.

Focus on pembrolizumab first line data(Keynote 001)

Median PFS was 6.1months in all treatedpatients and 12.5, 4.2and 3.5 mos in >50%,1-49% and <1% resp.

OS was not reached inall treated patients orin patients with ≥50% staining

16.2 months and 10.4in patients withstaining in 1%–49%and <1% of cells,

respectively

Rizvi, ASCO 2015

Phase III trials in 1st-line advanced NSCLC(selected)

Nivolumab

Pembrolizumab

MEDI4736

SOC=standard of care. ClinicalTrials.gov. http://www.clinicaltrials.gov/. Accessed August 2015.

KEYNOTE-042Pembrolizumab

SOC chemotherapy

Primary endpoint: OSPD-L1+ NSCLCN = 1240

Primary endpoints: OS,PFS

Treatment-naïve or recurrent NSCLCN = 1980

CheckMate 227

Nivolumab

Nivolumab + ipilimumab

Platinum-based chemotherapy

Primary endpoint: PFSTreatment-naïve or recurrent PD-L1+NSCLC N = 535

CheckMate 026Nivolumab

Investigator’s choice chemotherapy

KEYNOTE-024Pembrolizumab

Platinum-based chemotherapy

Primary endpoint: PFSPD-L1 strong NSCLCN = 300

Atezolizumab

IMpower 111Atezolizumab

Gemcitabine + cisplatin or carboplatin

Primary endpoint: PFSStage IV squamous PD-L1+ NSCLCN = 400

IMpower 150

Atezolizumab + carboplatin + paclitaxel

Bevacizumab + paclitaxel + carboplatin

Primary endpoint: PFSStage IV non-squamous NSCLCN = 1200

Atezolizumab + bev. + paclitaxel + carboplatin

IMpower 130Atezolizumab + carboplatin + nab-paclitaxel

Carboplatin + nab-paclitaxel

Primary endpoint: PFSStage IV non-squamous NSCLCN = 550

IMpower 110Atezolizumab

Carboplatin or carboplatin + pemetrexed

Primary endpoint: PFSStage IV non-squamous PD-L1+NSCLC N = 400

IMpower 131

Atezolizumab + carboplatin + nab-paclitaxel

Carboplatin + nab-paclitaxel

Primary endpoint: PFSStage IV squamous NSCLCN = 1200

Atezolizumab + carboplatin + paclitaxel

Primary endpoint: PFSAdvanced NSCLCN = 675

MYSTIC

MEDI4736

MEDI4736 + tremelimumab

SOC chemotherapy

IPI + Paclitaxel/Carboplatin IPI

Pbo + Paclitaxel/Carboplatin PboPrimary endpoint: OSSquamous NSCLC

N = 920CA184-104

IPI + Paclitaxel/Carboplatin IPI

Pbo+ Paclitaxel/Carboplatin PboPrimary endpoint: OSSquamous NSCLC

N = 867CA184-153

Ipilimumab

An

ti-P

D-1

/PD

-L1

An

ti-

CT

LA

-4

Thanks for your attention

Documents

Check point inhibitors for NSCLC: How does it work ... · Check point inhibitors for NSCLC: How does it work ... • History of nodular sclerosing Hodgkin ... WE could change this