ImmunoOncology in Lung Cancer

Lung Cancer – Taming through a ‘Novel Pathway’ #immunoncology!

Ashok .K. VaidMedical Oncology & Hematology

Medanta Cancer Institute : Medanta – The Medicity,Gurgaon (New Delhi), India

Excerpts from ASCO 2015

• Lung Cancer Background• Immunity and Cancer• Biomarkers- ASC0 2015• Advanced NSCLC• Other Malignancies

SCLC and mesothelioma

Lung Cancer Incidence and Mortality

• New cases in 2013: 228,190– 40% with stage IV disease at presentation

(~ 90,000)

• ~ 160,000 deaths in 2013, comparable to prostate, pancreas, breast, and colon cancer combined

• 5-year relative survival rate: 13% overall (2% for patients with distant-stage) disease

NCI. Non-small-cell lung cancer treatment (PDQ®). ACS. Cancer facts & figures: 2013.

Estimated Cancer Deaths by Site, 2013

Other Cancers Lung Cancer

180,000160,000

140,000

120,000

100,000

80,000

60,000

40,000

20,000

0

Lung cancer

Prostate

Pancreas

Breast

Colon

1975 1980 1985 1990 1995 2000 20050

5

10

15

20

Year of Diagnosis

5-ye

ar O

S (%

)

Gain in 5-year OS over the past 3 decades in lung cancer

http://seer.cancer.gov, Accessed Nov. 2014

History of Therapy in Advanced NSCLC: FDA Approval Dates

First lineSecond lineThird lineMaintenanceNot approved

1970 1980 1990 2000

MedianOS (mos)

12+

~ 6~ 2-4

BSC Single-agent platinum DoubletsBevacizumab + PC

Carboplatin*1989

ErlotinibPemetrexed

2004

Docetaxel1999

PaclitaxelGemcitabine

1998

Vinorelbine1994

Docetaxel2002

Bevacizumab2006

Gefitinib2003

Standard therapies

*Label does not include NSCLC-specific indication Pemetrexed

2008/2009

Histology-directed therapy

~ 8-10

Cisplatin*1978

1. FDA Web site. 2. NCCN. Clinical practice guidelines in oncology. v.3.2011. 3. Schrump, et al. Non-small cell lung cancer. In: Cancer: Principles and Practice of Oncology. 7th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2005.

Role of immune system in cancer prevention• Eliminate/ suppress viral

infections: protection from viral induced tumors.

• Prevent establishment of an inflammatory environment

• Identify and eliminate tumor cells based on the expression of tumor-specific antigens: cancer immuno surveillance

• Cytotoxic T cells play a key role in cancer immune response

Cytotoxic T cells play a key role in cancer immune response

• Regulated by a range of immune cells.

• T cells- potent mediators of anti-tumor immunity

• T cell immune response: – recognize a "non-self" target– Involves processing &

presentation– Cytotoxic T cells: effector cells– Activated, search of cells

bearing that unique MHC Class I + peptide

Cancer immunotherapy

CTLA-4: cytotoxic T lymphocyte associated protein 4PD-1: programed cell death protein 1Mellman Nature 2011

T cell response is regulated by co-stimulatory (“Go”)and co-inhibitory/checkpoint (“Stop”) factors

“Brakes”“Accelerator”

Immune checkpoint inhibitors

Attenuate T cell response

Promote T cell response

T cell regulation is important!Prevents immune mediated damage

Immune checkpoint inhibitorsPharmaceutical Compound Status

CTLA-4 inhibitor

BMS Ipilimumab Approved for melanoma

AZ/MedImmune Tremelimumab Phase III

PD-1 inhibitor

BMS Nivolumab Approved for melanoma, NSCLC (SCC)

MSD Pembrolizumab Approved for melanoma

Curetech Pidilizumab Phase II

Novartis PDR001 Phase I-II

PD-L1 inhibitor

Genentech/ Roche Atezolizumab Phase III

AZ/MedImmune Durvalumab Phase III

Merck Serono Avelumab Phase III

Biomarkers- ASCO 2015

Primary endpoint• OS

Study objective• To investigate the efficacy and safety of atezolizumab (MPDL3280A) in NSCLC and

correlation of response with PD-L1 expression on tumour-infiltrating immune cells (IC) and/or tumour cells (TC)

• PD-L1 expression was evaluated by IHC using the SP142 antibody assay• Patients were scored as TC0, 1, 2 or 3 and IC0, 1, 2 or 3

Spira et al. J Clin Oncol 2015; 33 (suppl): abstr 8010

Secondary endpoints• PFS, ORR, duration of response, safety

8010: Efficacy, safety and predictive biomarker results from a randomized phase II study comparing MPDL3280A vs docetaxel in 2L/3L NSCLC (POPLAR) – Spira AI et al

Stratification• PD-L1 IC expression (0 vs. 1 vs. 2 vs. 3)• Histology (squamous vs. non-squamous)• Prior chemotherapy regimens (1 vs. 2)

R

PD

Loss of clinical benefitKey patient inclusion criteria

• Metastatic or locally advanced NSCLC

• At least 1 prior platinum-based chemotherapy

(n=287) Docetaxel 75 mg/m2 q3w (n=143)

Atezolizumab 1200 mg IV q3w (n=144)

• Key results– Across the ITT interim population, survival was similar between atezolizumab and

docetaxel (HR 0.77; 95%CI 0.55, 1.06; p=0.11)– However, OS with atezolizumab increased with increasing PD-L1 expression (TC/IC ≥1);

those with <1% expression did not derive benefit relative to docetaxel



p=0.070

p=0.026

p=0.024

p=0.70

p=0.11

Interim OSSubgroup (% of enrolled patients)

TC3 or IC3 (16%)

TC2/3 or IC2/3 (37%)

TC1/2/3 or IC1/2/3 (68%)

TC0 or IC0 (32%)

ITT (N=287)

0.46

0.56

0.63

1.12

0.77

0.2 1 2Hazard ratioa

In favour of atezolizumab In favour of docetaxel

a Unstratified HR for subgroups and stratified HR for ITT. Data cut-off Jan 30, 2015

• Key results (cont.)– Patients with higher PD-L1 expression also had better outcomes with atezolizumab than with docetaxel (ORR 38% vs.

13% in patients with the highest levels)

– Atezolizumab was well tolerated with fewer treatment-related Grade 3/4 AEs (12% atezolizumab; 39% docetaxel) despite a longer treatment duration (3.7 vs. 2.1 months)

• Conclusions– Improved survival with atezolizumab was associated with increasing PD-L1 expression– PD-L1 is a predictive diagnostic biomarker that can be used to identify those patients with NSCLC who will

benefit most from atezolizumab therapy



TC3 or IC3 TC2/3 or IC2/3

TC1/2/3 or IC1/2/3

TC0 and IC0 ITT0

10

20

30

40

5038

2218

81513 15 18

1015

Atezolizumab (n=144)

Docetaxel (n=143)

OR

R (c

onfir

med

,R

EC

IST

v1.1

), %

Gainor et al. J Clin Oncol 2015; 33 (suppl): abstr 8012

8012: Clinical correlation and frequency of PD-L1 expression in EGFR-mutant and ALK-rearranged NSCLC – Gainor JF et al

• Study objective– To evaluate PD-L1 expression patterns and clinical outcomes in EGFR-mutant and ALK-

rearranged NSCLC patients receiving TKIs• Study design

– Retrospective analysis of IHC data of biopsy and resection specimens from patients with metastatic, EGFR-mutant (n=68) and ALK-rearranged (n=28), NSCLC. Expression of PD-L1 in >5% tumour cells was defined as positive. CD8+ tumour-infiltrating lymphocytes (TILs) were evaluated using a 4-tier grading system (0−3)

• Key results

– No significant difference was observed in PFS or OS between PD-L1 (+) and (-) patients. OS on ALK TKIs was shorter among PD-L1 (+) patients (p=0.045)

• Conclusion– EGFR-mutant and ALK-rearranged lung cancers can express PD-L1 and show

CD8+ immune infiltrates, but most do not have both. This may explain the low response rates observed with PD-1 inhibitors in never/light smokers

EGFR-mutant ALK-rearrangedn/N (%) Pre-TKI Post-TKI p Pre-TKI Post-TKI pPD-L1 (+) 9/62 (15) 16/64 (25) 0.181 11/21 (52) 3/14 (21) 0.089CD8+ TILs (2-3+) 12/62 (19) 13/65 (20) 1.000 6/18 (33) 0/14 (0) 0.024PD-L1 (+) and CD8+ TILs (2-3+) 3/61 (5) 8/64 (13) 0.207 3/18 (17) 0/14 (0) 0.238

7560: The association of T cells with survival in mesothelioma – Chee SJ et al

Chee et al. J Clin Oncol 2015; 33 (suppl): abstr 7560

• Study objective– To assess whether tumour infiltrating lymphocyte (TIL) density identifies patients with

mesothelioma and ongoing immune attack who may benefit from immune activation • Study design

– Tissue microarrays were performed on a consecutive series of 213 samples from patients with mesothelioma; slides were stained for CD3, CD4, CD8 and CD45RO

– The mean score was used to account for tumour heterogeneity• Key results

– There was no association between density of tumour infiltrating CD3 (p=0.224), CD4 (p=0.205) and CD8 (p=0.243) cells and survival outcomes

– Two variables were significantly associated with better survival:• High (>0.61) CD4:CD8 ratio (p=0.007)• Low CD45RO level (p=0.002)

• Conclusion– A high CD4:CD8 ratio and low density of CD45RO memory T cells are

associated with better survival in patients with mesothelioma

Advanced NSCLCLater lines

LBA109: Phase III, randomized trial (CheckMate 057) of nivolumab (NIVO)- PD 1 inhibitor- versus docetaxel in advanced non-SQ NSCLC – Paz-Ares L et al

Primary endpoint• OS

Secondary endpoints• ORR, PFS, safety, efficacy by PD-L1

expression, QoL

R

PD or toxicity

PD or toxicity

Stratification• Prior maintenance therapy• Line of therapy (2nd vs. 3rd)

Key patient inclusion criteria• Stage IIIB/IV non-squamous

NSCLC• Pre-treatment (archival or

recent) tumor samples available for PD-L1 testing

• ECOG PS 0–1• Failed 1 prior platinum

doublet(n=582)

Docetaxel 75 mg/m2 IV q3w

(n=290)

Nivolumab 3 mg/kg IV q2w

(n=292)

Study objective• To evaluate the efficacy and safety of nivolumab vs. docetaxel in patients with advanced

non-squamous NSCLC after failure of platinum-based doublet chemotherapy

Paz-Ares et al. J Clin Oncol 2015; 33 (suppl): abstr LBA109

LBA109: Phase III, randomized trial of nivolumab (NIVO) versus docetaxel in advanced (non-SQ) NSCLC – Paz-Ares L et al

• Key results– Nivolumab was associated with a 27% reduction in risk of death


OS

0 3 6 9 12 15 18 21 24 27

292 232 194 169 146 123 62 32 9 0290 244 194 150 111 88 34 10 5 0

Time (months)

Nivolumab

Docetaxel

1-year OS rate=51%

1-year OS rate=39%

Symbols represent censored observations

NivolumabDocetaxel

Number of Patients at Risk

OS

(%)

Nivolumab (n=292)

Docetaxel(n=290)

mOS, months 12.2 9.4

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

100

90

80

70

60

50

40

30

20

10

0

LBA109: Phase III, randomized trial of nivolumab (NIVO) versus docetaxel in advanced non-squamous cell (non-SQ) NSCLC – Paz-Ares L et al• Key results

• PD-L1 expressors benefitted more from nivolumab than PD-L1 non-expressors

– Nivolumab improved survival vs. docetaxel in previously treated patients with advanced non-squamous NSCLC with efficacy being correlated with PD-L1 expression


PD-L1 expression levelNivolumab

(n)Docetaxel

(n)Unstratisfied HR

(95% CI)Interaction

p-value*

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 at baseline 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 at baseline 61 66 1.06 (0.73, 1.56)

PD-L1 expressors

PD-L1 non-expressors

PD-L1 not quantifiable

0.25 0.5 1.0 2.0

Nivolumab Docetaxel

Next step

• Combination of immune targeted drugs

Study objective• To investigate the antitumour activity and tolerability of the combination of MEDI4736 (M)

and tremelimumab (T) in patients with advanced NSCLC who have failed to respond or relapsed after any line of therapy

Study design• Phase 1b, open-label, dose-escalation study in patients with advanced NSCLC• Treated with M (3, 10, 15, or 20 mg/kg q4w or 10 mg/kg q2w) and T (1, 3, or 10 mg/kg q4w

for 6 doses then q12w for 12 doses) administered for 12 months Key results

G, grade; D/C, discontinuation

3014: Phase Ib study of MEDI4736, a PD-L1 antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in advanced NSCLC – Antonia SJ et al

Antonia et al. J Clin Oncol 2015; 33 (suppl): abstr 3014

N (%)

M3q4wT1

n=3

M10q4wT1

n=3

M15q4wT1

n=18

M20q4wT1

n=18

M10q2wT1

n=17

M10q4wT3

n=3

M15q4wT3

n=14

M20q4wT3

n=6

M10q2wT3

n=11

M15q4wT10n=9

All cohortsn=102

Any AE 3 (100) 3 (100) 17 (94) 14 (78) 15 (88) 3 (100) 14 (100) 6 (100) 11 (100) 9 (100) 95 (93)Any G3/G4 AE 0 (0) 2 (67) 11 (61) 8 (44) 6 (35) 3 (100) 10 (71) 6 (100) 7 (64) 8 (89) 61 (60)Any deaths 0 (0) 1 (33) 3 (17) 2 (11) 2 (12) 0 (0) 3 (21) 2 (33) 1 (9) 1 (11) 15 (15)*SAE 1 (33) 2 (67) 11 (61) 7 (39) 4 (24) 2 (67) 10 (71) 6 (100) 5 (45) 8 (89) 56 (55)AE to D/C 1 (33) 1 (33) 4 (22) 1 (6) 2 (12) 2 (67) 5 (36) 4 (67) 3 (27) 4 (44) 27 (26)Related AE 1 (33) 3 (100) 11 (61) 9 (50) 12 (71) 3 (100) 12 (86) 5 (83) 10 (91) 8 (89) 74 (73)Related G3/G4 0 (0) 2 (67) 7 (39) 4 (22) 3 (18) 2 (67) 6 (43) 5 (83) 5 (45) 7 (78) 41 (40)Related deaths 0 (0) 1 (33)† 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) 1 (17)‡ 0 (0) 0 (0) 2 (2)Relates SAE 0 (0) 1 (33) 4 (22) 4 (22) 1 (6) 2 (67) 6 (43) 5 (83) 4 (36) 7 (78) 34 (33)Related AE to D/C 0 (0) 1 (33) 2 (11) 1 (6) 0 (0) 2 (67) 4 (29) 3 (50) 3 (27) 4 (44) 20 (20)

*Death excluding disease progression=8%; †Related death due to polymyositis (complications arising from drug-related myasthenia gravis); ‡Related death due to neuromuscular disorder. Red box=selected phase 3 dose.

3014: Phase Ib study of MEDI4736, a programmed cell death ligand-1 (PD-L1) antibody, in combination with tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) antibody, in patients (pts) with advanced NSCLC – Antonia SJ et al

KEY RESULTS

Lowest frequency of AEs was in the T1 cohorts and generally increased for doses above T1 (previous slide)

Treatment-related AEs across all cohortsGrade 3/4 occurred in 40% of patients (most frequently colitis, diarrhoea, elevated lipase and elevated liver function tests)31% of patients used corticosteroids and 20% discontinued therapy

Treatment-related AEs among patients treated at M20 q4w T1Grade 3/4 occurred in 22% of patients (most frequently diarrhoea, pruritus, rash and elevated AST/ALTs)17% of patients used corticosteroids and 6% discontinued therapy Clinical activity in patients with PD-L1 positive tumours in the T1 cohorts:ORR of 33% (95%CI 13, 59)DCR at ≥16 weeks of 44% (95%CI 14, 79)

Clinical activity in patients with PD-L1 negative tumours in the T1 cohorts:ORR of 38% (95%CI 14, 68)DCR at ≥16 weeks of 62% (95%CI 32, 86)


Conclusions The combination of M + T has a manageable safety profile with evidence of clinical activity,

including in PD-L1-negative disease The M20 q4w T1 dose combination will be investigated in phase 3 studies

AST, aspartate aminotransferase; ALT, alanine aminotransferase

Study objective• To evaluate the efficacy and safety of MEDI4736, a human IgG1 monoclonal anti-PD-L1

antibody, combined with gefitinib (G) in patients with NSCLCStudy design• Phase 1, dose escalation (n=10) and dose expansion (n=15) study • Expansion study undertaken in TKI-naïve patients with EGFR sensitising mutant NSCLC

• Arm 1: MEDI4736 10 mg/kg q2w plus G 250 mg qd• Arm 2: G 250mg qd for 4 weeks followed by MEDI4736 10 mg/kg q2w + G 250 mg qd

Key results• All patients in the dose-escalation phase demonstrated tumour reductions

Conclusions• MEDI4736 in combination with gefitinib shows acceptable tolerability and tumour reductions

with early signs of activity in TKI-naïve EGFR mutant population

3047: Safety and tolerability results from a phase I study of MEDI4736, (PD-L1 antibody), combined with gefitinib in patients (pts) with non-small-cell lung cancer (NSCLC) : – Creelan BC et al

Creelan et al. J Clin Oncol 2015; 33 (suppl): abstr 3047

Cohort A* (n=3)Cohort B† (n=6)

Cha

nge

in ta

rget

lesi

on

diam

eter

from

bas

elin

e, %

70605040302010

0–10–20–30–40–50

0 8 16 24 32 40 48Time (weeks)

xx

*Cohort A: G 250 mg qd + MEDI4736 3 mg/kg q2w;†Cohort B: G 250 mg qd + MEDI4736 10 mg/kg q2w

8011: Phase 1 study of pembrolizumab- PD 1 inhibitor- (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D – Patnaik A et al

• Study objective– To evaluate in a phase I study pembrolizumab + ipilimumab in patients with recurrent NSCLC of any histology (interim

results provided) • Key results

– As of 31 March 2015, 18 patients have been enrolled:• 3 in the pembrolizumab 10 mg/kg + ipilimumab 1 mg/kg, 3 in the pembrolizumab

10 mg/kg + ipilimumab 3 mg/kg, and 12 in the pembrolizumab 2 mg/kg + ipilimumab 1 mg/kg

– No DLTs have been reported– 15 patients experienced treatment-related AEs; 2 led to discontinuation (1 each with pembrolizumab 10 mg/kg +

ipilimumab 3 mg/kg and pembrolizumab 2 mg/kg + ipilimumab 1 mg/kg)

Patnaik et al. J Clin Oncol 2015; 33 (suppl): abstr 8011

• Key results (cont.)– Pembrolizumab + ipilimumab showed antitumour activity with all responses ongoing at

data cut-off

• Conclusions– Preliminary data demonstrate robust and durable antitumour activity with an

acceptable toxicity profile for pembrolizumab + ipilimumab in unselected patients with recurrent NSCLC

– The use of a lower ipilimumab dose did not appear to negatively impact efficacy

8011: Phase 1 study of pembrolizumab (pembro; MK-3475) plus ipilimumab (IPI) as second-line therapy for advanced non-small cell lung cancer (NSCLC): KEYNOTE-021 cohort D – Patnaik A et al

Patnaik et al. J Clin Oncol 2015; 33 (suppl): abstr 8011

Pembro 10 mg/kg + IPI 1 or 3 mg/kg,

(n=6)

Pembro 2 mg/kg + IPI 1 mg/kg,

(n=12) Total

(n=18)ORR, n (%) [95%CI] 3 (50) [12, 88] 4 (33) [10, 65] 7 (39) [17, 64]

DCR, n (%) [95%CI] 6 (100) [54, 100] 9 (75) [43, 94] 15 (83) [59, 96]

Best overall response, n (%) CR PR SD ≥6 weeks PD

1 (17)2 (33)3 (50)

0

04 (33)5 (42)3 (25)

1 (6)6 (33)8 (44)3 (17)

Other malignanciesSCLC and Mesothelioma

Primary endpoints• ORR per RECIST v1.1, safety

Study objective• To assess the efficacy and safety of pembrolizumab, an anti-PD-1 monoclonal antibody, in

patients with PD-L1+ SCLC

*Defined as membranous PD-L1 expression in ≥1% of cells in tumour nestsor positive bands in stroma;†Every 8 weeks for the first 6 months; every 12 weeks thereafter

7502: Pembrolizumab (MK-3475- PD 1 inhibior) in patients with extensive-stage SCLC: Preliminary safety and efficacy results from KEYNOTE-028 – Ott PA et al

Ott et al. J Clin Oncol 2015; 33 (suppl): abstr 7502

Secondary endpoints• PFS, OS, duration of response

Pembrolizumab 10 mg/kg q2w

CR, PR or SD

Key patient inclusion criteria• SCLC• PD-L1 positivity*• Failure of standard

therapy• ≥1 measurable lesion• ECOG PS 0 or 1• Absence of autoimmune

disease or interstitial lung disease

(n=20)

Treat for 24 months or

until PD/toxicity

Confirmed PD/

toxicity

Discontinue pembrolizumab

Response assessment†

• Key results– Pembrolizumab showed promising antitumour activity

– No unexpected toxicity• Most common AEs occurring in ≥2% were arthralgia and asthenia (15% of patients) followed by nausea and rash (10%)• One treatment-related death was reported (colitis) and one treatment-related discontinuation (grade 2 autoimmune

thyroiditis)• Conclusions

– Pembrolizumab was generally well tolerated and demonstrated preliminary promising antitumour activity in patients with PD-L1+ SCLC

7502: Pembrolizumab (MK-3475) in patients (pts) with extensive-stage small cell lung cancer (SCLC): Preliminary safety and efficacy results from KEYNOTE-028 – Ott PA et al

* Ott et al. J Clin Oncol 2015; 33 (suppl): abstr 7502

Best overall response n % 95%CI

ORR* 7 35 15−59

Complete response 0 0 0−17

Partial response 7 35 15−59

Stable disease 1 5 0−25

Progressive disease 9 45 23−69

No assessment# 3 15 3–38

Primary endpoint• ORR per RECIST v1.1

Study objective• To assess the efficacy and safety of nivolumab, an IgG4 PD-1 immune checkpoint inhibitor,

with or without ipilimumab, a CTLA-4 checkpoint inhibitor, in previously treated SCLC patients

7503: Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032 : Antonia SJ et al


Secondary endpoints• Safety, PFS, OS, biomarker analysis

Key patient inclusion criteria• SCLC• Progressive disease• ≥1 prior therapy including

first-line platinum-based therapy

• Unselected by PD-L1 expression

(n=128)

Nivolumab 1 mg/kg + ipilimumab 1 mg/kg IV q3w for 4 cycles (n=3)


Nivolumab 3 mg/kg IV q2w (n=40)


Nivolumab 3 mg/kg IV q2w

Data from this cohort were not presented

• Key results– Clinical responses occurred in patients regardless of PD-L1 expression

• Conclusions– Nivolumab alone or in combination with ipilimumab showed activity and durable responses in patients with SCLC and

progressive disease– Nivolumab alone or in combination with ipilimumab had a manageable safety profile– These regimens will be explored in future trials of patients with SCLC

7503: Phase I/II study of nivolumab with or without ipilimumab for treatment of recurrent small cell lung cancer (SCLC): CA209-032: Antonia SJ et al


Bes

t red

uctio

n fro

m b

asel

ine

inta

rget

lesi

on (%

)

150125100

7550250

–25–50–75

–100

Nivolumab + Ipilimumab

<1% PD-L1≥1% PD-L1Not evaluable*Confirmed responders

150125100755025

0–25–50–75

–100

Nivolumab

Evaluable samples (40 of 96) PD-L1 expression level, n (%)<1% ≥1%

Nivolumab (n=22) 15 (68) 7 (32)Nivolumab + ipilimumab (n=18) 12 (67) 6 (33)

Side effects of immunotherapy

Hypophysitis

Thyroiditis

Adrenal insufficiencyEnterocolitis

Dermatitis, itch, vitiligo, alopecia

Motor & sensory neuropathy

Hepatitis

Pneumonitis

Pancreatitis

Arthritis

Ocular: scleritis/uveitis

Renal toxicity: GNLower incidence of imAEs with PD-1/PD-L1 inhibitors compared with Ipilimumab (but not devoid of them) Most frequent toxicities reported are mild fatigue, rash, pruritis, diarrhoea and colitis

Conclusion

1. Immunotherapies represent a new pillar of treatment for NSCLC.2. PD-L1 is a potential predictive biomarker.3. Development of biomarker key to further development as a single

agent and in combination with other therapies.4. Unique side effects consistent with the immune mechanism of action.

MOVING AHEAD!

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ImmunoOncology in Lung Cancer

Education