LBA71 - First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (uMPM): 4-year update from CheckMate 743

Background

In the randomized, phase 3 CheckMate 743 study (NCT02899299), NIVO + IPI significantly prolonged OS vs chemo in pts with uMPM. Identifying pts with uMPM who could benefit from immunotherapy is an unmet need. Here, we report clinical results and exploratory biomarker analyses from CheckMate 743 at 4y minimum follow-up (min f/u).

Methods

Pts with previously untreated uMPM, stratified by histology and sex, were randomized 1:1 to receive NIVO (3 mg/kg Q2W) + IPI (1 mg/kg Q6W) for up to 2 y, or chemo (Q3W) for ≤ 6 cycles. Primary endpoint (EP) was OS; secondary EPs included PFS and ORR; exploratory EPs were safety and biomarker analyses. OS was assessed by baseline (BL) soluble mesothelin (sMESO) levels (high, mid, low by ELISA-based assay) and MPM-specific tumor suppressor mutations (TP53, BAP1, SETD2, NF2, LATS2 using whole-exome sequencing).

Results

At 47.5-month min f/u (database lock [DBL] 6 May 2022), NIVO + IPI continued to show OS benefit vs chemo with 4y OS rates of 16.8% vs 10.7%; 4y PFS rates were 9.0% vs 0%, respectively (Table). High (vs low or mid) BL sMESO level was associated with shorter OS in both arms; NIVO + IPI showed a trend of improved OS vs chemo across BL sMESO levels (HRs [95% CI], high: 0.72 [0.53–0.98], mid: 0.77 [0.56–1.06], low: 0.77 [0.56–1.05], respectively). OS favored NIVO + IPI vs chemo for both wild-type (HRs = 0.67–0.72) and MPM-specific tumor suppressor mutation subgroups (HRs = 0.41–0.55), except SETD2 mutation (HR = 1.37). Consistent with the prior DBL, the most common grade 3/4 immune-mediated adverse events with NIVO + IPI were hepatitis (5%), diarrhea/colitis (4%), and rash (3%). Table: LBA71

Efficacy outcomes with NIVO + IPI vs chemo

^aPer blinded independent central review;^bCalculated in patients with a response (NIVO + IPI, n = 119; chemo, n = 134);^cAll pts either had disease progression or were censored by month 39. DOR, duration of response; ORR, objective response rate; OS, overall survival; PFS, progression-free survival.

Conclusions

With 4y min f/u, NIVO + IPI continued to provide long-term, durable OS benefit vs chemo in pts with uMPM. No new safety signals were seen. High BL sMESO levels were prognostic for poor OS. OS benefit with NIVO + IPI vs chemo was generally observed regardless of MPM-specific tumor suppressor mutations.

Clinical trial identification

NCT02899299.

Editorial acknowledgement

All authors contributed to and approved the presentation; writing and editorial assistance were provided by Thai Cao, MS, of Evidence Scientific Solutions, Inc., and funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb (Princeton, NJ) and Ono Pharmaceutical Company Ltd. (Osaka, Japan).

Funding

Bristol Myers Squibb.

Disclosure

G. Zalcman: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Roche, MSD, Pfizer, Boehringer, Inventiva, Paredox Therapeutics, Lilly; Financial Interests, Personal, Other, Travel/Accommodations: AstraZeneca, Bristol Myers Squibb, AbbVie, Roche, MSD, Pfizer, Lilly. Y. Oulkhouir: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb. R. Cornelissen: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, MSD, Spectrum; Financial Interests, Personal, Speaker’s Bureau: Roche. L. Greillier: Financial Interests, Personal, Advisory Board: AbbVie, AstraZeneca, BMS, MSD, Novartis, Sanofi, Takeda, Roche; Financial Interests, Personal, Invited Speaker: Lilly, Pfizer, Roche; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, BMS, MSD, Novartis, Sanofi, Takeda, Pfizer, PharmaMar. J.R. Rodriguez Cid: Financial Interests, Personal, Invited Speaker: Roche, MSD, Bristol Myers Squibb, AstraZeneca, Takeda, Amgen, Eli lilly, Pfizer, Bayer, Boehringer Ingelheim, Merck; Financial Interests, Personal, Advisory Role: Roche, MSD, Bristol Myers Squibb, AstraZeneca, Takeda, Amgen, Eli lilly, Pfizer, Bayer, Boehringer Ingelheim, Merck; Financial Interests, Personal, Research Grant: Roche, MSD, Bristol Myers Squibb, AstraZeneca, Takeda, Amgen, Celltrion, Daichi Sankyo, Eli lilly, Pfizer, Bayer . J. Mazieres: Financial Interests, Personal, Invited Speaker: Roche, AstraZeneca, Bristol Myers Squibb, MSD, Daiichi, Novartis, Amgen; Financial Interests, Personal, Advisory Board: Roche, AstraZeneca, Pierre Fabre, Takeda, Bristol Myers Squibb, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Lilly, Merck; Financial Interests, Personal, Research Grant: Roche, AstraZeneca, Pierre Fabre, Bristol Myers Squibb; Non-Financial Interests, Personal, Principal Investigator: Roche, AstraZeneca, Pierre Fabre, Takeda, Bristol Myers Squibb, MSD, Jiangsu Hengruii, Blueprint, Daiichi, Novartis, Amgen, Sanofi, Pfizer, Merck. A.K. Nowak: Financial Interests, Institutional, Other, Clinical trial steering committee: Roche Pharmaceuticals; Financial Interests, Personal, Other, Bayer Pharmaceuticals: Bayer Pharmaceuticals; Financial Interests, Personal, Other, Clinical trial steering committee: Boehringer Ingelheim, Merck Sharp Dohme; Financial Interests, Institutional, Other, Clinical trials consulting, payment to institution: Douglas Pharmaceuticals, Atara Biotherapeutics; Financial Interests, Personal, Other, Clinical trials consulting.: Pharmabcine; Financial Interests, Personal, Other, Clinical trials consulting: Trizell Ltd; Financial Interests, Institutional, Funding, Research funding to institution: AstraZeneca, Douglas Pharmaceuticals; Other, Other, Travel funding to attend ASCO 2018: Boehringer Ingelheim; Other, Other, Travel funding to attend ASCO 2019: AstraZeneca. A. Tsao: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Eli Lilly, Genentech, Roche, Novartis, Ariad, EMD Serono, Merck, Seattle Genetics, AstraZeneca, Boehringer-Ingelheim, Sellas Life Science, Takeda, Epizyme, Huron; Financial Interests, Personal, Research Grant: Bristol Myers Squibb, Eli Lilly, Genentech, Ariad, EMD Serono, Merck, Boehringer-Ingelheim, Takeda, Epizyme, Millennuim, Polaris. N. Fujimoto: Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb, ONO Pharmaceutical; Financial Interests, Personal, Advisory Board: ONO Pharmaceutical. S. Peters: Financial Interests, Institutional, Advisory Board: Vaccibody, Takeda, Seattle Genetics, Sanofi, Roche/Genentech, Regeneron, Phosplatin Therapeutics, PharmaMar, Pfizer, Novartis, Mirati, Merck Serono, MSD, Janssen, Incyte, Illumina, IQVIA, GlaxoSmithKline, Gilhead, Genzyme, Foundation Medicine, F-Star, Eli Lilly, Debiopharm, Daiichi Sankyo, Boehringer Ingelheim, Blueprint Medicines, Biocartis, Bio Invent, BeiGene, Bayer, BMS, AstraZeneca, Arcus, Amgen, AbbVie, iTheos, Novocure; Financial Interests, Institutional, Invited Speaker: Takeda, Sanofi, Roche/Genentech, RTP, Pfizer, PRIME, PER, Novartis, Medscape, MSD, Imedex, Illumina, Fishawack, Eli Lilly, Ecancer, Boehringer Ingelheim, AstraZeneca, BMS, OncologyEducation, RMEI, Mirati; Financial Interests, Personal, Other, Associate Editor Annals of Oncology: Elsevier; Financial Interests, Institutional, Invited Speaker, MERMAID-1: AstraZeneca; Financial Interests, Institutional, Invited Speaker, MERMAID-2, POSEIDON, MYSTIC: AstraZeneca; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering committee CheckMate 743, CheckMate 73L, CheckMate 331 and 451: BMS; Financial Interests, Institutional, Invited Speaker, RELATIVITY 095: BMS; Financial Interests, Institutional, Invited Speaker, BGB-A317-A1217-301/AdvanTIG-301: Beigene; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair ZEAL-1: GSK; Financial Interests, Institutional, Invited Speaker, Clinical Trial steering Committee PEARLS, MK-7684A: MSD; Financial Interests, Institutional, Invited Speaker, Clinical Trial Steering Committee SAPPHIRE: Mirati; Financial Interests, Institutional, Invited Speaker, LAGOON: Pharma Mar; Financial Interests, Institutional, Invited Speaker, phase 1/2 trials: Phosplatin Therapeutics; Financial Interests, Institutional, Invited Speaker, Clinical Trial Chair Skyscraper-01; chair ALEX; steering committee BFAST; steering committee BEAT-Meso; steering committee ImPower-030, IMforte: Roche/Genentech; Financial Interests, Institutional, Invited Speaker, Phase 2 Inupadenant with chemo: iTeos; Non-Financial Interests, Officer, ESMO President 2020-2022: ESMO; Non-Financial Interests, Officer, Council Member & Scientific Committee Chair: ETOP/IBCSG Partners; Non-Financial Interests, Officer, Vice-President Lung Group: SAKK; Non-Financial Interests, Other, Involved in Swiss politics: Swiss Political Activities; Non-Financial Interests, Officer, President and Council Member: Ballet Béjart Lausanne Foundation; Non-Financial Interests, Principal Investigator, Involved in academic trials: ETOP / EORTC / SAKK; Non-Financial Interests, Member: Association of Swiss Physicians FMH (CH), ASCO, AACR, IASLC; Non-Financial Interests, Leadership Role, ESMO President: ESMO; Non-Financial Interests, Member, Vice-President Lung Group: SAKK; Non-Financial Interests, Leadership Role, Vice -President: SAMO; Non-Financial Interests, Member, Association of Swiss interns and residents: ASMAC/VSAO. A.S. Mansfield: Financial Interests, Institutional, Funding, Study funding, article processing charges: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Study funding: Novartis, Verily; Financial Interests, Institutional, Other, Grant reviewer: Rising Tide; Financial Interests, Institutional, Advisory Role: TRIPTYCH Health Partners Expert Think Tank; Financial Interests, Institutional, Other, Steering Committee: Janssen, Johnson & Johnson Global Services; Financial Interests, Institutional, Invited Speaker: BeiGene, Chugai Pharmaceutical Co Ltd (Roche), Miami International Mesothelioma Symposium, AXIS Medical Education, Inc.; Financial Interests, Institutional, Invited Speaker, Moderator: Ideology Health LLC (formerly Nexus Health Media); Financial Interests, Personal, Invited Speaker, CME Activity: Antoni van Leeuwenhoek Kanker Instituut; Financial Interests, Institutional, Invited Speaker, CME Activity: Intellisphere LLC (OncLive Summit Series), Answers in CME; Financial Interests, Institutional, Other, Travel/Accomodations: Roche; Financial Interests, Institutional, Advisory Board: AbbVie, AstraZeneca, Bristol Myers Squibb, Genentech/Roche; Non-Financial Interests, Leadership Role, Director: Mesothelioma Applied Research Foundation. S. Popat: Financial Interests, Personal, Advisory Board: Boehringer Ingelheim, Novartis, Amgen, Janssen, Daiichi Sankyo, AstraZeneca, Bayer, BMS, Blueprint, Merck Serono, Guardant Health, Beigene, Takeda, Lilly, Seattle Genetics, Turning Point Therapeutics, Xcovery, GlaxoSmithKline, MSD, Pfizer, Sanofi; Financial Interests, Personal, Expert Testimony: Roche; Financial Interests, Personal, Invited Speaker: Medscape, VJ Oncology, Touch Medical; Financial Interests, Institutional, Invited Speaker: AstraZeneca, Ariad, Roche, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Trizel, GlaxoSmithKline, Takeda, Turning Point Therapeutics, Roche, Janssen, BMS, Lilly; Financial Interests, Personal, Other, Journal Deputy Editor, Lung Cancer: Elsevier; Financial Interests, Institutional, Other, Sub-investigator: Amgen; Financial Interests, Institutional, Other, Sub-Investigator: MSD, Blueprint, Seattle Genetics; Financial Interests, Institutional, Research Grant: Guardant Health; Non-Financial Interests, Leadership Role, Chair of Steering Committee, Unpaid: British Thoracic Oncology Group; Non-Financial Interests, Officer, Thoracic Faculty, Unpaid: European Society of Medical Oncology; Non-Financial Interests, Leadership Role, Foundation Council Member, Unpaid: European Thoracic Oncology Platform; Non-Financial Interests, Advisory Role, Mesothelioma Task-force Member, Unpaid: International Association for the Study of Lung Cancer; Non-Financial Interests, Invited Speaker, Unpaid: Mesothelioma Applied Research Foundation; Non-Financial Interests, Advisory Role, Honorary Clinical Advisor, Unpaid: ALK Positive UK; Non-Financial Interests, Advisory Role, Research Advisory Group Member, Unpaid: Ruth Strauss Foundation; Non-Financial Interests, Advisory Role, Scientific Adivsory Board Member, Unpaid: Lung Cancer Europe. A. Nassar: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Bushong: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. T. Spires: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. L. Eccles: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb. P. Baas: Financial Interests, Institutional, Advisory Board: BMS, MSD, Beigene; Financial Interests, Institutional, Research Grant: MSD, BMS. All other authors have declared no conflicts of interest.