LBA65 - First-line nivolumab (NIVO) plus ipilimumab (IPI) vs chemotherapy (chemo) in patients (pts) with unresectable malignant pleural mesothelioma (MPM): 3-year update from CheckMate 743

Background

In the randomized phase 3 CheckMate 743 study (NCT02899299), NIVO + IPI significantly prolonged overall survival (OS) vs chemo in pts with unresectable MPM. Here we report updated efficacy and safety with a 3-y minimum follow-up (f/u), as well as novel biomarker analyses.

Methods

Pts with untreated MPM, stratified by histology (epithelioid vs non-epithelioid) and sex, were randomized 1:1 to NIVO 3 mg/kg Q2W + IPI 1 mg/kg Q6W (≤ 2 y) or to chemo Q3W (6 cycles). The primary endpoint was OS; safety and biomarker assessments were prespecified exploratory endpoints. OS association with a 4-gene inflammatory gene expression signature (CD8A, PD-L1, STAT-1, LAG-3) was estimated by RNA sequencing and categorized as high vs low relative to median score. Lung immune prognostic index (LIPI) score was based on baseline (BL) derived neutrophil-to-lymphocyte ratio and lactate dehydrogenase levels.

Results

With a minimum f/u of 35.5 mo (database lock [DBL] 7 May 2021), NIVO + IPI continued to provide OS benefit vs chemo (HR 0.75, 95% CI 0.63–0.90; Table). In exploratory biomarker analyses, median OS was longer for pts with high vs low inflammatory gene signature score (21.8 vs 16.8 mo) in the NIVO + IPI arm; this signature score was not associated with prolonged OS for chemo. OS showed a trend favoring NIVO + IPI vs chemo across good, intermediate, and poor BL LIPI subgroups; HR (95% CI), 0.78 (0.60–1.01), 0.76 (0.57–1.01), and 0.83 (0.44–1.57), respectively. Grade 3–4 treatment-related adverse events occurred in 30.7% (NIVO + IPI) and 32.0% (chemo) of pts; no increase was reported from the previous DBL. Table: LBA65

Efficacy outcomes with NIVO + IPI vs chemo

^aPer blinded independent central review; ^bCalculated in patients with a response (NIVO + IPI, n = 120; chemo, n = 133). DOR, duration of response; ORR, objective response rate; PFS, progression-free survival.

Conclusions

With a 3-y minimum f/u, NIVO + IPI continued to provide survival benefit vs chemo in pts with unresectable MPM despite pts being off therapy for 1 y; no new safety signals were observed. Exploratory analyses suggest that a high inflammatory gene signature score may correlate with improved survival benefit with NIVO + IPI.

Clinical trial identification

NCT02899299; 14 September 2016.

Editorial acknowledgement

All authors contributed to and approved the presentation; writing and editorial assistance were provided by Nick Patterson, PhD, of Caudex, London, UK, 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

S. Peters: Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): AbbVie; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Amgen; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Amgen; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): AstraZeneca; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): AstraZeneca; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): AstraZeneca; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Bayer; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Beigene; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Biocartis; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Biodesiex; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Boehringer Ingelheim; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Boehringer Ingelheim; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Bristol Myers Squibb; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Clovis; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Clovis; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Daiichi Sankyo; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Debiopharm; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): ecancer; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): ecancer; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Eli Lilly; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Eli Lilly; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Foundation Medicine; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): GlaxoSmithKline; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Illumina; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Illumina; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Illumina; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Imedex; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): IQVIA; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Incyte; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Janssen; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Lilly; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Medscape; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Medscape; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Merck Sharp & Dohme; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Merck Sharp & Dohme; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Merck Sharp & Dohme; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Merck Serono; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Merck Serono; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Merrimack; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Mirati; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Novartis; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Novartis; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Novartis; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): PharmaMar; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Phosplatin Therapeutics; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Phosplatin Therapeutics; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): PER; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): PER; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Pfizer; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Pfizer; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Pfizer; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): PRIME; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): PRIME; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Regeneron; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Roche/Genentech; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Roche/Genentech; Financial Interests, Institutional, Research Grant, Received honoraria (all fees to institution): Roche/Genentech; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): RTP; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): RTP; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Sanofi; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Sanofi; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Seattle Genetics; Financial Interests, Institutional, Advisory Role, Received honoraria (all fees to institution): Takeda; Financial Interests, Institutional, Speaker’s Bureau, Received honoraria (all fees to institution): Takeda. A. Scherpereel: Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Speaker’s Bureau: AstraZeneca; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Speaker’s Bureau: Merck Sharp & Dohme; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Merck Sharp & Dohme. R. Cornelissen: Financial Interests, Personal, Speaker’s Bureau: Roche; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Speaker’s Bureau: Pfizer; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Spectrum. Y. Oulkhouir: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: AstraZeneca. L. Greillier: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Advisory Board: AbbVie; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Novartis. T. Talbot: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel/expenses: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau: Bristol Myers Squibb. I. Monnet: Non-Financial Interests, Personal, Invited Speaker, Congress: ESMO 2019: Pfizer; Non-Financial Interests, Personal, Invited Speaker, Congress: ESMO 2018: Roche. S. Hiret: Financial Interests, Personal and Institutional, Advisory Board: Takeda; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca. P. Baas: Financial Interests, Institutional, Advisory Role, Fee to hospital: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant, Fee to hospital: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Fee to hospital: Takeda; Financial Interests, Institutional, Advisory Role, Fee to hospital: BeiGene; Financial Interests, Institutional, Advisory Role, Fee to hospital: AstraZeneca; Financial Interests, Institutional, Advisory Role, Fee to hospital: Merck Sharp & Dohme; Financial Interests, Institutional, Advisory Role, Fee to hospital: Roche; Financial Interests, Institutional, Advisory Role, Fee to hospital: Epizyme; Financial Interests, Institutional, Advisory Role, Fee to hospital: Trizell; Financial Interests, Institutional, Advisory Role, Fee to hospital: Daiichi Sankyo. A.K. Nowak: Financial Interests, Personal, Advisory Role, clinical trials consultant: Bayer; Financial Interests, Personal, Advisory Role, clinical trials consultant: Pharmabcine; Financial Interests, Personal, Advisory Role, clinical trials consultant: Trizell; Financial Interests, Personal, Advisory Board, clinical trial steering committee: Roche; Financial Interests, Personal, Advisory Board, clinical trial steering committee: Boehringer Ingelheim; Financial Interests, Personal, Other, Travel/Accommodation/Expenses: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, clinical trial steering committee: Merck Sharp & Dohme; Financial Interests, Personal and Institutional, Advisory Role, clinical trials consultant: Douglas Pharmaceuticals; Financial Interests, Personal and Institutional, Research Grant: Douglas Pharmaceuticals; Financial Interests, Personal and Institutional, Advisory Role, clinical trials consultant: Atara Biotherapeutics; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: AstraZeneca. N. Fujimoto: Financial Interests, Personal, Advisory Role: Ono Pharmaceutical; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb. A.S. Tsao: Financial Interests, Institutional, Advisory Board: Genentech; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Ariad; Financial Interests, Institutional, Advisory Board: EMD Serono; Financial Interests, Institutional, Research Grant: EMD Serono; Financial Interests, Institutional, Advisory Board: Merck; Financial Interests, Personal and Institutional, Advisory Board: Seattle Genetics; Financial Interests, Personal and Institutional, Research Grant: Seattle Genetics; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Sellas Life Science; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Institutional, Research Grant: Millennium; Financial Interests, Institutional, Research Grant: Polaris; Financial Interests, Institutional, Research Grant: Epizyme. A.S. Mansfield: Financial Interests, Personal and Institutional, Advisory Role: AbbVie; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: AbbVie; Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role: Genentech; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Verily; Financial Interests, Institutional, Member of the Board of Directors: Mesothelioma Applied Research Foundation; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Institutional, Advisory Role: Janssen; Financial Interests, Institutional, Research Grant: Mark Foundation; Financial Interests, Institutional, Research Grant: NIH. S. Popat: Financial Interests, Personal and Institutional, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Research Grant: Amgen; Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Beigene; Financial Interests, Personal, Advisory Board: Blueprint; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Principal Investigator: Boehringer Ingelheim; Financial Interests, Personal and Institutional, Advisory Board: Daiichi Sankyo; Financial Interests, Personal and Institutional, Principal Investigator: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Guardant Health; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck KGaA; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Advisory Board: Roche; Financial Interests, Personal and Institutional, Principal Investigator: Roche; Financial Interests, Personal and Institutional, Advisory Board: Takeda; Financial Interests, Personal and Institutional, Principal Investigator: Takeda; Financial Interests, Institutional, Principal Investigator: Ariad; Financial Interests, Institutional, Principal Investigator: Celgene; Financial Interests, Institutional, Principal Investigator: GlaxoSmithKline; Financial Interests, Institutional, Research Grant: Merck Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Trizel; Financial Interests, Institutional, Principal Investigator: Turing Point Therapeutics. X. Zhang: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. N. Hu: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. D. Balli: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. J. Sanzari: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. G. Zalcman: Financial Interests, Personal and Institutional, Advisory Role: AstraZeneca; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: AstraZeneca; Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: Roche; Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Other, Travel/Accommodation/Expenses: Roche; Financial Interests, Personal, Advisory Role: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Role: Da Volterra; Financial Interests, Personal and Institutional, Advisory Role: Inventiva; Financial Interests, Personal and Institutional, Research Grant: Inventiva; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: Boehringer Ingelheim; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: AbbVie; Financial Interests, Institutional, Other, Travel/Accommodation/Expenses: Pfizer. All other authors have declared no conflicts of interest.