Background

Detection of residual disease post-NA treatment (tx) using ctDNA may indicate response and post-surg relapse risk. We profiled ctDNA and describe ctDNA dynamics in pts with NSCLC pre- and post-NA tx with atezo (anti–PD-L1) and post-surg in the LCMC3 study.

Methods

Pts (N=181) with stage IB to select IIIB NSCLC received 2 cycles of NA atezo before surg. Tumour tissue–informed, germline-corrected ctDNA was measured pre- and post-atezo and post-surg using the AVENIO Oncology Surveillance Test (ctDNA+ defined as ctDNA detection index ≤0.05). We correlated quantitative ctDNA levels and ctDNA presence with major pathologic response (MPR; primary endpoint), pathologic response, change in tumour size and disease-free survival (DFS).

Results

126 pts had sufficient tissue to test, of which 106 (84%) had tumour variants suitable for monitoring. Of these, ctDNA was detected in 72% of pre-atezo (n=101), 56% of post-atezo (n=102) and 10% of post-surg samples (n=49). Median ctDNA levels (range) dropped from 3 (0-4448) mean tumour molecules/mL plasma (mtm/mL) pre-atezo to 0.5 (0-406) mtm/mL post-atezo and 0 (0-35) mtm/mL post-surg (all paired comparisons P<0.01). Greater ctDNA reduction post-atezo was seen in pts with MPR vs non-MPR (median log₂ fold change −4.8 vs 0.3, P<0.001). Reduced ctDNA levels post-atezo were also associated with pathologic response (P<0.001, r=0.38) and reduction in radiographic tumour size (P<0.001, r=0.42). 2-yr DFS rate for pts who were ctDNA– vs ctDNA+ post-surg was 75% vs 40% (HR, 3.6; 95% CI: 1.0, 13.1; P=0.054). In 64 pts with non-squamous tumours, higher disease stage was associated with higher rates of pre-atezo ctDNA+ status and ctDNA levels (all P<0.05).

Conclusions

>60% of pts with resectable lung cancers had sufficient tissue, trackable tumour variants, and were ctDNA+ pre-atezo. ctDNA reductions post-atezo correlated with pathologic response and reduced radiographic tumour size. 2-yr DFS was better in pts who were ctDNA– post-surg. Combining changes in ctDNA with pathologic and radiographic assessment may provide a thorough measurement of response to NA therapy, and may inform management of early NSCLC pts.

Clinical trial identification

NCT02927301.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Derrick Afful, PhD and Christopher Lum, PhD of Health Interactions Inc, and funded by Genentech, Inc.

Legal entity responsible for the study

Genentech, Inc.

Funding

Genentech, Inc.

Disclosure

M.G. Kris: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Editorial Support: Genentech; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Janssen. J.M. Grindheim: Financial Interests, Personal, Full or part-time Employment: Genentech, Inc; Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech. J.E. Chaft: Financial Interests, Personal, Other, editorial/ medical writing assistance: Genentech; Financial Interests, Personal, Other, Consultant: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant: Genentech; Financial Interests, Personal, Other, Consultant: Merck. J.M. Lee: Financial Interests, Personal, Other, Editorial/ medical writing Support: Novartis; Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Research Grant: AstraZeneca; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting Fees: Genentech; Financial Interests, Personal, Other, Consulting Fees: Novartis; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Genentech; Financial Interests, Personal, Speaker’s Bureau: Novartis; Financial Interests, Personal, Speaker’s Bureau: eCancer; Financial Interests, Personal, Speaker’s Bureau: Medscape; Financial Interests, Personal, Other, meeting attendance support: AstraZeneca; Financial Interests, Personal, Other, meeting attendance support: Genentech; Financial Interests, Personal, Leadership Role, Steering or Executive Committee for Clinical Trials: AstraZeneca; Financial Interests, Personal, Leadership Role, Steering or Executive Committee for Clinical Trials: Genentech; Financial Interests, Personal, Leadership Role, Steering or Executive Committee for Clinical Trials: Novartis. B.E. Johnson: Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Cannon Medical Systems; Financial Interests, Personal, Advisory Board: Hengrui Therapeutics; Financial Interests, Personal, Advisory Board: Checkpoint Therapeutics; Financial Interests, Personal, Advisory Board: Boston Pharmaceuticals; Financial Interests, Personal, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: G1 Therapeutics; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Jazz Pharmaceuticals; Financial Interests, Personal, Advisory Board: Janssen Scientific; Financial Interests, Personal, Other, Consultant: Novartis; Financial Interests, Personal, Other, Dana-Farber Cancer Institute: Dana-Farber Cancer Institute. V.W. Rusch: Financial Interests, Institutional, Other, Institutional Clinical Trial: Genelux, Inc.; Financial Interests, Institutional, Other, Institutional clinical trial: Genentech; Financial Interests, Personal, Other, Travel reimbursement for robotic mentoring: Intuitive Surgical; Financial Interests, Personal, Other, Travel and meeting prep reimbursement for Co-Chair of Thoracic Malignancy Staging Committee: NIH/Coordinating Center for Clinical Trials. P.A. Bunn: Financial Interests, Personal, Other, editorial/ medical writing support: Genentech; Financial Interests, Personal, Other, Consulting fees: AstraZeneca; Financial Interests, Personal, Other, Consulting fees: Ascentage; Financial Interests, Personal, Other, Consulting fees: CStone; Financial Interests, Personal, Other, Consulting fees: Imidex; Financial Interests, Personal, Other, Consulting fees: Viecure; Financial Interests, Personal, Other, Consulting fees: Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Ascentage; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: CStone; Financial Interests, Personal, Advisory Board: Imidex; Financial Interests, Personal, Advisory Board: Viecure; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Leadership Role: Verastem,.H. Pass: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Research Grant: Delfi; Financial Interests, Personal, Research Grant: Micronoma; Financial Interests, Personal, Royalties: NCI (cell lines); Financial Interests, Personal, Speaker’s Bureau: PER; Financial Interests, Personal, Speaker’s Bureau: RTP; Financial Interests, Personal, Other, Patent: IL8 for Lung Cancer; Financial Interests, Personal, Leadership Role, Steering committee for Skyscaper: Genentech; Financial Interests, Personal, Leadership Role, Steering committee for IMpower: Genentech. E. Schum: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Genentech. J. Carlisle, M. Weyant: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech. A. Nicholas, A. Johnson, D. Shames: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. I. I Wistuba: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Research Grant: Genentech; Financial Interests, Personal, Research Grant: HTG Molecular; Financial Interests, Personal, Research Grant: DepArray; Financial Interests, Personal, Research Grant: Merck; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Research Grant: Medimmune; Financial Interests, Personal, Research Grant: Adaptive; Financial Interests, Personal, Research Grant: Adaptimmune; Financial Interests, Personal, Research Grant: EMD Serono; Financial Interests, Personal, Research Grant: Pfizer; Financial Interests, Personal, Research Grant: Takeda; Financial Interests, Personal, Research Grant: Amgen; Financial Interests, Personal, Research Grant: Karus; Financial Interests, Personal, Research Grant: Johnson & Johnson; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Iovance; Financial Interests, Personal, Research Grant: 4D; Financial Interests, Personal, Research Grant: Novartis; Financial Interests, Personal, Research Grant: Akoya; Financial Interests, Personal, Other, Consulting Fees: Genentech/Roche; Financial Interests, Personal, Other, Consulting fees: Bayer; Financial Interests, Personal, Other, Consulting Fees: Bristol Myers Squibb; Financial Interests, Personal, Other, Consulting Fees: AstraZeneca; Financial Interests, Personal, Other, Consulting Fees: Pfizer; Financial Interests, Personal, Other, Consulting fees: HTG Molecular; Financial Interests, Personal, Other, Consulting fees: Asuragen; Financial Interests, Personal, Other, Consulting Fees: Merck; Financial Interests, Personal, Other, Consulting fees: GlaxoSmithKline; Financial Interests, Personal, Other, Consultant Fees: Guardant Health; Financial Interests, Personal, Other, Consultant fees: Flame; Financial Interests, Personal, Other, Consultant Fees: Novartis; Financial Interests, Personal, Other, Consutant fees: Sanofi; Financial Interests, Personal, Other, Consultant Fees: Daiichi Sankyo; Financial Interests, Personal, Other, Consultant Fees: Amgen; Financial Interests, Personal, Other, Consultant fees: Oncocyte; Financial Interests, Personal, Other, Consultant fees: MSD; Financial Interests, Personal, Speaker’s Bureau: Medscape; Financial Interests, Personal, Speaker’s Bureau: MSD; Financial Interests, Personal, Speaker’s Bureau: Genentech/Roche; Financial Interests, Personal, Speaker’s Bureau: Platform Health; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: Merck. D.P. Carbone: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Other, Consultant: Bristol Myers Squibb; Financial Interests, Personal, Other, Consultant: Bristol Myers Squibb KK (Japan); Financial Interests, Personal, Other, Consultant: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Inc.; Financial Interests, Personal, Advisory Board: Eisai; Financial Interests, Personal, Advisory Board: EMD Serono/Merck; Financial Interests, Personal, Advisory Board: Flame Biosciences; Financial Interests, Personal, Other, Consultant: FENIX; Financial Interests, Personal, Other, Consultant: Genentech/Roche; Financial Interests, Personal, Other, Consultant: GI Therapeutics/ Intellisphere; Financial Interests, Personal, Advisory Board: Glaxo-Smith Kline; Financial Interests, Personal, Other, Consultant: Glaxo-Smith Kline; Financial Interests, Personal, Advisory Board: Gritstone; Financial Interests, Personal, Other, Consultant: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Other, Consultant: Mirati; Financial Interests, Personal, Other, Consultant: Novocure; Financial Interests, Personal, Other, Consultant: OncoCyte; Financial Interests, Personal, Other, Consultant: OncoHost; Financial Interests, Personal, Other, Consultant: Piper Sandler; Financial Interests, Personal, Other, Consultant: Roche China; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Other, Consultant: Seattle Genetics; Financial Interests, Personal, Other, editorial/ medical writng support: Genentech. K. Schulze: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech; Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. D.J. Kwiatkowski: Financial Interests, Personal, Other, Editorial/ medical writing Support: Genentech.

Background

IMpower010 met its primary DFS endpoint in PD-L1 TC ≥1% (SP263) stage II-IIIA NSCLC patients (pts) and all stage II-IIIA NSCLC pts (Felip, Lancet 2021). We report exploratory DFS outcomes by additional PD-L1 subgroups and EGFR/ALK status; we also assessed ctDNA status as a potential biomarker in this setting.

Methods

Eligible pts with resected (R0) stage IB-IIIA NSCLC received up to four 21-day cycles of chemo and were then randomised 1:1 to atezo 1200 mg Q3W (16 cycles) or BSC. Stratification factors included PD-L1 status by SP142. We analysed DFS by PD-L1 expression at different TC levels (SP263; <1%, ≥1%, 1-49%, ≥50%) and by EGFR/ALK status in stage II-IIIA pts. Plasma samples for ctDNA testing were collected after surgery but before adjuvant chemo and analysed using the Natera Signatera RUO assay.

Results

Of 1005 randomised pts, 979 (97%) were evaluable by SP263; of these, 859 had stage II-IIIA NSCLC. SP263 subgroups were balanced between arms. DFS improvement with atezo vs BSC was seen in all PD-L1+ subgroups (Table). When EGFR/ALK+ pts were excluded, numerical improvements in DFS HRs were seen in all PD-L1 subgroups except TC ≥50%, which remained at 0.43. 600 pts were ctDNA evaluable; of these, 534 had stage II-IIIA NSCLC. ctDNA+ prevalence increased with disease stage (IB, 9%; II, 14%; IIIA, 29%). ctDNA+ vs ctDNA− stage II-IIIA pts had worse prognosis; improved DFS with atezo vs BSC was seen in both ctDNA+ and ctDNA− stage II-IIIA pts, with greater benefit in PD-L1 TC ≥1% vs <1% pts.

Conclusions

Although SP142 was used to stratify by PD-L1 status, SP263 PD-L1 subgroups were balanced between arms. DFS HRs numerically improved in most PD-L1 subgroups when pts with known EGFR/ALK+ NSCLC were excluded. ctDNA positivity (Natera Signatera) appeared to be a poor prognostic factor for DFS; however, atezo showed DFS benefit in both ctDNA+ and ctDNA− stage II-IIIA pts in the PD-L1 TC ≥1% subgroup. Table: 2O

Stage II-IIIA pts

Clinical trial identification

NCT02486718.

Editorial acknowledgement

Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD of Health Interactions and funded by F. Hoffmann-La Roche, Ltd.

Legal entity responsible for the study

F. Hoffmann-La Roche, Ltd.

Funding

F. Hoffmann-La Roche, Ltd.

Disclosure

C. Zhou: Financial Interests, Personal, Invited Speaker: Roche China, Lily China, Boehringer Ingelheim, Sanofi, C-Stone, Qilu, Hengrui, Innovent Biologics, LUYE Pharma, TopAlliance Bioscience Inc, Amoy Diagnostics. M. Das Thakur, W. Zou: Financial Interests, Personal, Full or part-time Employment: Roche. M.K. Srivastava: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. H. Xu: Financial Interests, Personal, Full or part-time Employment: Roche; Financial Interests, Personal, Stocks/Shares: Roche. M. Ballinger: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. E. Felip: Financial Interests, Personal, Advisory Board: Pfizer, Merck Serono, Merck Sharp & Dohme, F. Hoffman-La Roche, Eli Lilly, Bristol Myers Squibb, AstraZeneca, AbbVie, Amgen, Bayer, Blue Print Medicines, Glaxo Smith Kline, Medical Trends, Peptomyc, Puma, Sanofi Genzyme, Syneos Health, Takeda; Financial Interests, Personal, Invited Speaker: PrIME Oncology, Springer, Touch Medical, Pfizer, Merck Serono, Janssen, Merck Sharpe & Dohme, F. Hoffmann-La Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Eli Lilly; Financial Interests, Personal, Other, Grant: Grant for Medical Oncology Innovation (GOI); Financial Interests, Personal, Other, Grant: Fundacion Merck Salud. H. Wakelee: Financial Interests, Personal, Invited Speaker: AstraZeneca, Janssen, Daiichi Sankyo, Blueprint, Mirati, Helsinn; Financial Interests, Personal, Invited Speaker: Fishawack Facilitate LTD, Medscape, Research to Practice, MJH Holdings, Axis Medical Education, Nexus Oncology; Financial Interests, Personal, Other, Discussion of new data at conferences: Curio Science; Financial Interests, Personal, Writing Engagements: UpToDate; Financial Interests, Institutional, Other, Local PI for Clinical Trials: ACEA Biosciences, Arrys Therapeutics, AstraZeneca/Medimmune, Bristol Myers Squibb, Clovis Oncology, Novartis, Seagen, Xcovery; Financial Interests, Institutional, Other, Coordinating PI for Clinical Trial: Celgene; Financial Interests, Institutional, Other, Steering Committee Member for clinical trial: Genentech/Roche, Merck; Financial Interests, Personal, Officer, President Elect: International Association for the Study of Lung Cancer (IASLC); Financial Interests, Personal, Leadership Role, Executive Committee: ECOG-ACRIN. N.K. Altorki: Other, Institutional, Research Grant: NCI, DoD, AZ LLC, Janssen. M. Reck: Financial Interests, Personal, Speaker’s Bureau: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche; Financial Interests, Personal, Other, Consultancy: Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Lilly, Mirati, Merck, MSD, Novartis, Pfizer, Sanofi, Roche. H. Tanaka: Financial Interests, Personal, Speaker’s Bureau: Chugai Pharmaceutical, AstraZeneca, Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Chugai Pharmaceutical, AstraZeneca, MSD, Bristol Myers Squibb, Ono Pharmaceutical. S. McCune: Financial Interests, Institutional, Principal Investigator: Genentech. V. McNally: Financial Interests, Personal, Full or part-time Employment: Genentech/Roche; Financial Interests, Personal, Stocks/Shares: Genentech/Roche. E. Bennett: Financial Interests, Personal, Full or part-time Employment: Roche/Genentech. B. Gitlitz: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. S. Novello: Financial Interests, Personal, Invited Speaker: Novartis, Pfizer, Takeda, Roche, AstraZeneca, Boehringer Ingelheim, Beigene, AMG, Eli Lilly, Glaxo Smith Kline; Financial Interests, Personal, Advisory Board: Sanofi, AstraZeneca, Eli Lilly, Glaxo Smith Kline, Novartis, Pfizer, Takeda, Roche. All other authors have declared no conflicts of interest.

Background

Endogenous retrovirus (ERV) elements represent genomic footprints of ancestral retroviral infections within the human genome. Previous studies have demonstrated that ERV transcription has been associated with increased immunogenicity in cancers. This study focused on the identification of an ERV signature for predict PD-1 blockade response in advanced clear cell renal cell carcinoma (ccRCC).

Methods

We obtained ERV mRNA profiles from 3 clinical trials of the anti-PD-1 antibody nivolumab in advanced ccRCC (named RCC_CheckMate), and The Cancer Genome Atlas database (TCGA-KIRC). Identify innate immunity-related ERVs in all the cohorts. Univariate Cox proportional hazards regression analysis and LASSO Cox model were performed to identify and construct the prognostic ERV signature. Time-dependent receiver operating characteristic, the Kaplan-Meier curve was used to assess the prognostic capacity of the ERV signature.

Results

In this study, the RCC_CheckMate cohort included 181 advanced ccRCC patients from CheckMate 009 (NCT01358721), CheckMate 010 (NCT01354431), and CheckMate 025 (NCT01668784). RCC_CheckMate cohort was divided into the train (n=129 pts) and test cohort (n=52 pts). This study identified a prognostic signature based on 27 innate immunity-related ERV mRNAs. In the train cohort, the median OS in the high- and low-risk groups was 20.7 vs 46.3 months (HR=0.36 (0.23 - 0.57); P = 4e-06), respectively. In the test cohort, the median OS in the high- and low-risk groups were 16.9 vs NR (not reach) months (HR=0.31 (0.15 - 0.65); P = 0.001). In order to validate ERV signature at independently cohort, 83 advanced RCC patents selected from TCGA-KIRC, the median OS in the high- and low-risk groups were 15.1 vs 30.6 months (HR=0.55 (0.33 - 0.89); P = 0.01). In all the advanced ccRCC patients, the low-risk group showed significantly better survival compared with the high-risk group.

Conclusions

Our study established a novel ERV signature which works as a valid predictive and prognostic biomarker for immunotherapy-treated advanced ccRCC patients.

Clinical trial identification

Pseudonymized individual participant data from CheckMate 009 (NCT01358721), CheckMate 010 (NCT01354431) and CheckMate 025 (NCT01668784).

Legal entity responsible for the study

The authors.

Funding

This research was funded by the National Natural Science Foundation of China (Grant No. 81660512), the National Natural Science Foundation of Guizhou Province (Grant No. ZK2021-YB435), Research Programs of Science and Technology Commission Foundation of Zunyi City (Grant Nos. HZ2019-11, HZ2019-07), Research Programs of Health Commission Foundation of Guizhou Province (Grant Nos. gzwjkj2019-1-073, gzwjkj2019-1-172), Lian Yun Gang Shi Hui Lan Public Foundation (Grant No. HL-HS2020-92). AW Medical Company Limited received startup funding from the University Development Fund of University of Macau.

Disclosure

All authors have declared no conflicts of interest.

Background

In CheckMate 227 Part 1 (NCT02477826), 1L NIVO + IPI demonstrated durable and long-term clinical benefit vs chemo in patients (pts) with aNSCLC at a 4-y minimum follow-up. Here, we report exploratory analyses on the outcomes of pts by KRAS, STK11, and KEAP1 mutation status.

Methods

Eligible pts were treatment naive, with stage IV/recurrent NSCLC, no known EGFR/ALK alterations, ECOG PS 0–1. Pts with PD-L1 ≥ 1% were randomized 1:1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W, NIVO 240 mg Q2W, or chemo; pts with PD-L1 < 1% were randomized 1:1:1 to NIVO + IPI, NIVO 360 mg Q3W + chemo, or chemo. For pts in the all-randomized population (PD-L1 ≥ 1% and < 1%) with non-squamous (NSQ) NSCLC and tissue samples evaluable for mutational analysis, the FoundationOne CDx^TM assay was used to identify KRAS, STK11, and KEAP1 mutations. Assessment of OS, PFS, and response rates with NIVO + IPI vs chemo by mutation status was exploratory. Minimum OS follow-up was 49.4 mo.

Results

Of 1166 pts randomized to NIVO + IPI or chemo, 838 had NSQ histology, 475 of whom were mutation-evaluable. Of the mutation-evaluable pts, 34%, 16%, and 8% had KRAS, STK11, and KEAP1 mutations, respectively. With the exception of histology, baseline characteristics in the mutation-evaluable pts were generally similar to the NSQ and all-randomized populations and balanced between treatment arms. Consistent with the NSQ and all-randomized populations, OS was improved with NIVO + IPI vs chemo in the mutation-evaluable patients (median OS, 20.2 vs 16.3 mo; HR, 0.75 [95% CI, 0.61–0.93]; 4-y OS rates, 32% vs 20%). NIVO + IPI improved OS vs chemo in pts with or without KRAS, STK11, or KEAP1 mutations (Table); however, subgroups with mutations were small. Additional efficacy outcomes will be presented.Table: 4O

Conclusions

In these exploratory analyses, survival benefit with NIVO + IPI vs chemo was observed regardless of KRAS, STK11, and KEAP1 mutation status in pts with aNSCLC.

Clinical trial identification

NCT02477826 June 23, 2015.

Editorial acknowledgement

All authors contributed to and approved the presentation; writing and editorial assistance were provided by Brooke Bouza, PhD, of Caudex, New York City, NY, USA, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb (Princeton, NJ).

Funding

Bristol Myers Squibb.

Disclosure

S.S. Ramalingam: Financial Interests, Personal, Advisory Role: Amgen, Genentech/Roche, Lilly, Bristol Myers Squibb, AstraZeneca, Merck, Takeda, GlaxoSmithKline, Eisai, Daiichi Sankyo, Sanofi; Financial Interests, Personal, Research Grant: EMD Serono, Genmab, Advaxis, Tesaro, Bristol Myers Squibb, AstraZeneca, Merck, Takeda, GlaxoSmithKline. D. Balli: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. T. Ciuleanu: Financial Interests, Personal, Advisory Role: AstraZeneca, Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis/GlaxoSmithKline, Roche, Sanofi, Servier, Pfizer; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: AstraZeneca, Amgen, Astellas, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Janssen, MSD, Novartis/GlaxoSmithKline, Roche, Sanofi, Servier, Pfizer. A. Pluzanski: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Bristol Myers Squibb. M. Schenker: Financial Interests, Personal, Funding, Fees for clinical activities: Amgen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Eli Lilly, Gilead, GlaxoSmithKline, Merck, MSD, Mylan, Novartis, Pfizer, Pharma Mar, Regeneron, Roche, Serono. R. Bernabe Caro: Financial Interests, Personal, Advisory Role: AstraZeneca, Bristol Myers Squibb, MSD, Takeda, Pfizer; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Research Grant: Roche. K.H. Lee: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, AstraZeneca, Pfizer, Eli Lilly. C. Audigier-Valette: Financial Interests, Personal, Advisory Role: AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Ipsen, Lilly, Novartis, Pfizer, Roche; Financial Interests, Personal, Other, Consultancy: AstraZeneca, Boehringer Ingelheim, Ipsen, Lilly, Novartis, Pfizer, Roche. M. Hellmann: Financial Interests, Personal, Advisory Role: Merck, Bristol Myers Squibb, AstraZeneca, Genentech, Roche, Natera, Mirati, Shattuck Labs, Immunai, Blueprint Medicines, Achilles, Arcus, Adagene, Adicet, DaVolaterra, Eli Lilly, Genzyme/Sanofi, Janssen, Regeneron, Instil Bio, Mana Therapeutics, Pact Phar; Financial Interests, Personal, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Shattuck Labs, Immunai, Arcus, Factorial; Financial Interests, Institutional, Licensing Fees, patent filed by MSKCC (PCT/US2015/062208) which has received licensing fees from PGDx: MSKCC. L. Paz-Ares: Financial Interests, Personal, Leadership Role: Genomica, ALTUM sequencing; Non-Financial Interests, Personal, Speaker’s Bureau: MSD Oncology, Bristol Myers Squibb, Roche / Genentech, Pfizer, Lilly, Merck Serono; Financial Interests, Personal, Other, Travel / Accommodations / Expenses: Roche, AstraZeneca, MSD, Bristol Myers Squibb, Pfizer, Takeda; Financial Interests, Personal, Other, Honoraria: MSD Oncology, Bristol Myers Squibb, Roche / Genentech, Pfizer, Lilly, Merck Serono, AstraZeneca, Pharma Mar, Novartis, Celgene, Amgen, Sanofi, Ipsen, Servier, Bayer, Blueprint Medicines, Mirati Therapeutics, Takeda; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, AstraZeneca, Pharma Mar, Kura Oncology, MSD. M. Reck: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche, Samsung; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Boehringer Ingelheim; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: AbbVie, Amgen, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Merck, MSD, Novartis, Pfizer, Roche. H. Borghaei: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Lilly, Celgene, Genentech, Pfizer, Boehringer Ingelheim, EMD Serono, Trovagene, Novartis, Merck, AstraZeneca, Genmab, Regeneron, Cantargia AB, BioNTech AG, AbbVie, Pharma Mar, Takeda, Amgen, HUYA Bioscience International, Sonnet, Rge; Financial Interests, Personal, Other, Honoraria: Bristol Myers Squibb, Lilly, Celgene, Pfizer, Merck, Axiom Biotechnologies; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Lilly, Celgene, Merck, Millenium; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Bristol Myers Squibb, Lilly, Celgene, Genentech, Novartis, Merck, Clovis Oncology; Financial Interests, Personal, Stocks/Shares: Sonnet, Rgenix, Nuclaei; Financial Interests, Personal, Other, Data Safety Monitoring Board: Takeda, University of Pennsylvania, Incyte. J.R. Brahmer: Financial Interests, Personal, Advisory Role: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, Merck, GlaxoSmithKline, Sanofi; Financial Interests, Personal, Other, Consulting: Amgen, AstraZeneca, Bristol Myers Squibb, Genentech, Merck, GlaxoSmithKline, Sanofi, Regeneron; Financial Interests, Personal, Other, Honoraria: Genentech; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Genentech; Financial Interests, Personal, Other, Data & Safety Monitoring Board Committee: GlaxoSmithKline, Sanofi. K. O’byrne: Financial Interests, Personal, Advisory Role: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva, Takeda, Yuhan, Natera, Tristar; Financial Interests, Personal, Other, Honoraria: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva, Takeda, Yuhan, Natera, Tristar; Financial Interests, Personal, Speaker’s Bureau: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Novartis, Janssen, Teva; Non-Financial Interests, Personal, Other, Travel / Accommodation / Expenses: Pfizer, Roche, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, MSD, Lilly Oncology, Janssen; Non-Financial Interests, Personal, Speaker’s Bureau: Foundation Medicine; Financial Interests, Personal, Stocks/Shares: RepLuca Pharmaceuticals, Carpe Vitae Pharmaceuticals, DGC Diagnostics; Non-Financial Interests, Personal, Member of the Board of Directors: Carpe Vitae Pharmaceuticals. P. Tran, T. Spires: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. W.J. Geese, S. Agrawal: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. All other authors have declared no conflicts of interest.