LBA43 - 10-y survival outcomes from the phase III CheckMate 067 trial of nivolumab plus ipilimumab in advanced melanoma

Background

In CheckMate 067, improved survival with nivolumab plus ipilimumab (NIVO + IPI) or NIVO alone v IPI has been demonstrated in patients (pts) with advanced melanoma. We now provide the final CheckMate 067 results (minimum f/u 10 y), the longest reported in a phase 3 study of an anti–programmed death (PD)-1–based therapy for any tumor type.

Methods

Pts with untreated advanced melanoma (N = 945) were randomly assigned 1:1:1 and stratified by PD-ligand (L)1 status, BRAF mutation status, and metastasis stage to receive NIVO (1 mg/kg) + IPI (3 mg/kg) Q3W for 4 doses, followed by NIVO (3 mg/kg) Q2W; NIVO (3 mg/kg) Q2W + placebo; or IPI (3 mg/kg) Q3W for 4 doses + placebo until progression or unacceptable toxicity. Co-primary endpoints were OS and PFS with NIVO + IPI or NIVO v IPI; melanoma-specific survival (MSS) was an exploratory endpoint.

Results

After a 10-y minimum f/u, median OS was 71.9 mo with NIVO + IPI, 36.9 mo with NIVO, and 19.9 mo with IPI. OS HRs were 0.53 (95% CI, 0.44–0.65) with NIVO + IPI v IPI and 0.63 (0.52–0.76) for NIVO v IPI, and benefit was consistent across subgroups (including PD-L1 expression and BRAF mutation status). Median MSS was not reached (NR) with NIVO + IPI (> 120 mo), 49.4 mo with NIVO, and 21.9 mo with IPI. In pts who had PFS for ≥ 3 y, 10-y MSS rates were 96% with NIVO + IPI, 97% with NIVO, and 88% with IPI. Only 8 pts, 4 in the NIVO + IPI arm and 4 in the NIVO arm, progressed beyond 60-mo of f/u. For pts in the NIVO + IPI arm who discontinued treatment during induction due to a treatment-related adverse event, 10-y OS rates were the same as the ITT group (43%) and MSS rates were similar (50% v 52%). Table: LBA43

Conclusions

Final results from CheckMate 067 continue to demonstrate a sustained, long-term survival benefit across subgroups in the NIVO-containing arms, underscoring how checkpoint inhibitors have transformed the long-term prognosis for pts with advanced melanoma. There is now a potential for cure in pts responsive to these treatments.

Clinical trial identification

NCT01844505.

Editorial acknowledgement

Professional medical writing and editorial assistance were provided by Adam J. Santanasto, PhD, MPH and Michele Salernitano of Ashfield MedComms, an Inizio company, and funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb.

Funding

Supported by Bristol Myers Squibb, grant P30CA008748 to Jedd D. Wolchok from the National Cancer Institute, and a grant to James Larkin from the National Institute for Health Research Royal Marsden–Institute of Cancer Research Biomedical Research Centre.

Disclosure

J. Larkin: Financial Interests, Personal, Invited Speaker: BMS, Pfizer, Roche, Pierre Fabre, AstraZeneca, Novartis, EUSA Pharma, MSD, Merck, GSK, Ipsen, Aptitude, Eisai, Calithera, Ultimovacs, Seagen, Goldman Sachs, eCancer, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, RGCP, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. V. Chiarion Sileni: Financial Interests, Personal, Other, Travel, registration, and accommodation to attend ASCO annual meetings: Pierre-Fabre; Financial Interests, Personal, Invited Speaker: Pierre Fabre, Immunocore; Financial Interests, Personal, Other, Medical Congress Travel, registration and accommodation: Sanofi. C. Gaudy Marqueste: Financial Interests, Personal, Advisory Board: BMS, Pierre Fabre, MSD; Financial Interests, Personal, Invited Speaker: BMS, Pierre Fabre; Financial Interests, Institutional, Local PI: BMS, MSD, Pfizer, Amgen, GSK, Roche, Novartis, Pierre Fabre, Replimune, Jansen, Kartos, IFX, Huyabio, Regeneron, IO Biotech, Philogen, Sotio, Kinnate, AstraZeneca, Day One biopharmaceuticals, Sairopa, Catalyst, Sanofi, Immunocore; Other, Travel expenses: BMS, Pierre Fabre, MSD. P. Rutkowski: Financial Interests, Personal, Invited Speaker, honoraria for lectures: MSD, BMS, Pierre Fabre; Financial Interests, Personal, Advisory Board: MSD, BMS, Pierre Fabre, Merck, Sanofi, Blueprint Medicines, Philogen; Financial Interests, Personal, Invited Speaker: Merck, Sanofi, Novartis, AstraZeneca; Financial Interests, Institutional, Research Grant, research grant for ISS: Pfzer; Financial Interests, Institutional, Funding, research grant for institution: BMS; Non-Financial Interests, Member of Board of Directors: Polish Society of Surgical Oncology; Non-Financial Interests, Member of Board of Directors, President: Polish Oncological Society. T.M. Medina: Financial Interests, Institutional, Local PI: BMS, Merck, TriSalus, Genentech, Iovance, Replimune, Regeneron, Ultimovacs, Moderna, BioAtla, Pfizer, DayOne Biopharmaceuticals; Non-Financial Interests, Member: ASCO, SITC. C.D. Lao: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb; Financial Interests, Personal, Research Funding: Bristol Myers Squibb. D. Schadendorf: Financial Interests, Personal, Invited Speaker: BMS, MSD, Merck Serono, Sanofi, Neracare, SunPharma; Financial Interests, Personal, Advisory Board: BMS, Novartis, MSD, Immunocore, Pierre Fabre, Sanofi/Regeneron, Pfizer, Philogen, Neracare, InFlarX, BioAlta, Daiichi Sanyko, NoviGenix, Anaveon, AstraZeneca, PamGene, BioNTech, Immatics, CureVac, Erasca, Formycon, Replimune, Seagen, SunPharma, Ultimovacs; Financial Interests, Personal, Steering Committee Member: Novartis, BMS, MSD; Financial Interests, Institutional, Coordinating PI: Novartis, BMS, MSD, Pierre Fabre; Financial Interests, Institutional, Research Grant: BMS, MSD; Financial Interests, Institutional, Local PI: Sanofi, Philogen; Non-Financial Interests, Member of Board of Directors: EORTC-MG; Non-Financial Interests, Leadership Role, Founding member and SC chair: European Melanoma Registry (EuMelaReg). R. Dummer: Financial Interests, Personal, Other, Consulting and/or advisory role: Novartis, Merck Sharp & Dohme (MSD), Bristol Myers Squibb (BMS), Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome, Regeneron, MaviVAX SA, T3 Pharma, Pfizer, Simcere. P. Queirolo: Financial Interests, Personal, Advisory Role: Regeneron, Sanofi, BMS, MSD, Novartis, Pierre Fabre, Sun Pharma. J. Walker: Financial Interests, Institutional, Advisory Board, Consulting fee - Payment to professional corporation: Bristol Myers Squibb, Regeneron, Pfizer; Financial Interests, Personal, Other, Support to attend ESMO 2023: Pfizer. M.O. Butler: Financial Interests, Personal, Advisory Board: BMS, Merck, Novartis, Adaptimmune, Iovance, GSK, Sanofi, laRoche Possey, Pfizer, Medison, IDEAYA, Regeneron; Financial Interests, Personal, Invited Speaker: BMS, Merck, Novartis, Sanofi, Pfizer; Financial Interests, Personal, Advisory Board, Safety Review Committee: Adaptimmune; Financial Interests, Institutional, Other, Conduct Clinical Trial: TCR2, Novartis, Sanofi, Immunocore, GSK, Pfizer, Merck, Bristol Myers Squibb, Regeneron, AstraZeneca, Adaptimmune, Ideaya Biosciences, Amgen, Instil Bio, Turnstone Biologics, Iovance, Ankara; Financial Interests, Institutional, Research Grant, support clinical trial: Merck; Financial Interests, Institutional, Funding, support clinical trial: Takara Bio; Financial Interests, Institutional, Funding, support quality improvement project: Novartis. I. Marquez-Rodas: Financial Interests, Personal, Advisory Board: BMS, MSD, Novartis, Pierre Fabre, Roche, GSK, AstraZeneca, Celgene, Regeneron, Sanofi, Merck Serono, Highligth Therapeutics, Bioline Rx, Sun Pharma, Immunocore; Financial Interests, Personal and Institutional, Coordinating PI, GEM1802 clinical trial: Pierre Fabre; Financial Interests, Institutional, Coordinating PI, GEM1801 clinical study: Novartis, BMS, Roche, Pierre Fabre, Incyte, MSD; Financial Interests, Institutional, Coordinating PI, National coordinator of Spotlight 203 clinical trial: Highlight Therapeutics; Non-Financial Interests, Member of Board of Directors: Spanish Melanoma Group. J.B.A.G. Haanen: Financial Interests, Institutional, Advisory Board: Bristol Myers Squipp, Achilles Therapeutics, Immunocore, Gadeta, Ipsen, Merck Sharpe & Dohme, Merck Serono, Pfizer, Molecular Partners, Novartis, Roche, Sanofi, Instil Bio, Iovance Biotherapeutics, AstraZeneca; Financial Interests, Institutional, Advisory Board, SAB member: BioNTech, PokeAcel, T-Knife; Financial Interests, Personal, Advisory Board, SAB member: Neogene Therapeutics, Sastra Cell Therapy; Financial Interests, Personal, Advisory Board: Third Rock Venture, Scenic, CureVac, Imcyse; Financial Interests, Personal, Stocks/Shares: Neogene Therapeutics; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, BioNTech US, Merck Sharpe & Dohme, Amgen, Novartis, Asher Bio, Sastra Cell Therapy; Non-Financial Interests, Member: ASCO, AACR, SITC; Other, Editor-in-Chief IOTECH: ESMO; Other, Editorial Board ESMO Open: ESMO; Other, Editorial Board: Kidney Cancer. M. Askelson: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb; Financial Interests, Personal, Stocks or ownership: Bristol Myers Squibb. F..S. Hodi: Financial Interests, Personal, Advisory Role: Bristol Myers Squibb, Merck, Novartis, Compass Therapeutics, Apricity, Bicara, Checkpoint Therapeutics, Bioentre, Gossamer, Iovance, Catalym, Immunocore, Kairos, Rheos, Bayer, Zumutor, Corner Therapeutics, Puretech, Curis, AstraZeneca, Solu Therapeutics; Financial Interests, Personal, Advisory Board: Apricity; Financial Interests, Personal, Stocks or ownership: Apricity, Bicara, Checkpoint Therapeutics, Solu Therapeutics; Financial Interests, Personal, Other, Patent number: 10106611, Antibodies against EDIL3 and methods of use thereof: Methods for Treating MICA-Related Disorders (#20100111973), Tumor antigens and uses thereof (#7250291), Angiopoiten-2 Biomarkers Predictive of Anti-immune checkpoint response (#20170248603), Compositions and Methods for Identification, Assessment, Preve; Financial Interests, Personal, Research Funding: Bristol Myers Squibb, Merck, Genentech, Seattle Genetics; Financial Interests, Personal, Principal Investigator: PI of ECOG Trial EA6141. J.D. Wolchok: Financial Interests, Personal, Other, Consulting fees: Bristol Myers Squibb, Apricity, Ascentage Pharma, AstraZeneca, CellCarta, Bicara Therapeutics, Chugai, Daiichi Sankyo, Dragonfly, Imvaq, Psioxus, Takeda, Tizona, Trishula Therapeutics, Xenimmune; Financial Interests, Institutional, Research Funding: Enternome; Financial Interests, Personal, Other, Royalties & Licensed: Xenogeneic DNA Vaccines, Newcastle Disease viruses for Cancer Therapy; Financial Interests, Personal, Other, Royalties: Myeloid-derived suppressor cell (MDSC) assay, prediction of responsiveness to treatment with immunomodulatory; Financial Interests, Personal, Other, Licensed: Anti-PD1 Antibody, Anti-CTLA4 antibodies, Anti-GITR antibodies and methods of use thereof; Non-Financial Interests, Personal, Other, Data safety board - Uncompensated: Immunocore; Non-Financial Interests, Personal, Other, Melanoma advisory board - uncompensated: ScanCell; Financial Interests, Personal, Other, Board of Directors: AACR, Ludwig Institute for Cancer Research; Financial Interests, Personal, Other, Treasurer: SITC; Financial Interests, Personal, Stocks or ownership: Apricity, Ascentage Pharma, Arsenal IO/ CellCarta, Imvaq, Psioxus, Tizona, Xenimmune, Maverick, Georgiamune. All other authors have declared no conflicts of interest.