LBA44 - Pembrolizumab vs ipilimumab in advanced melanoma: 10-year follow-up of the phase III KEYNOTE-006 study

Background

Pembrolizumab (pembro) had superior efficacy compared with ipilimumab in patients (pts) with ipilimumab-naive advanced melanoma in the phase 3 KEYNOTE-006 study (NCT01866319); 10-year follow-up data are presented, including from pts who received second-course pembro.

Methods

Pts eligible for KEYNOTE-006 had unresectable stage III or IV melanoma and ≤1 prior line of therapy excluding CTLA-4 or PD-(L)1 inhibitors. Pts were randomly assigned to pembro 10 mg/kg Q2W or Q3W for ≤2 y or ipilimumab 3 mg/kg Q3W for 4 cycles. After KEYNOTE-006 ended, pts could transition to the KEYNOTE-587 extension study. Eligible pts could receive a second course of pembro for ≤1 y in KEYNOTE-006 or KEYNOTE-587. The primary end point of KEYNOTE-587 was OS. Modified PFS (censored at the last known alive date) on first-course pembro or ipilimumab and on second-course pembro were exploratory. Data for the pembro arms were pooled.

Results

834 pts were randomly assigned to pembro (n = 556) or ipilimumab (n = 278) in KEYNOTE-006, of whom 211 transitioned to KEYNOTE-587 (pembro, n = 159; ipilimumab, n = 52). For the 211 pts who transitioned to KEYNOTE-587, median time from study entry in KEYNOTE-006 to KEYNOTE-587 data cutoff (May 1, 2024) was 123.7 mo (range, 122.0-127.3). Median OS was 32.7 mo (95% CI, 24.5-41.6) for pembro vs 15.9 mo (95% CI, 13.3-22.0) for ipilimumab (HR, 0.71 [95% CI, 0.60-0.85]); 10-year OS rates were 34.0% and 23.6%, respectively. In pts who completed ≥94 weeks of pembro (n = 103), median OS from week 94 was not reached (NR; 95% CI, NR-NR); 8-year OS rate was 80.8%. OS HRs favored pembro in all subgroups, including pts with poor prognostic features. Median modified PFS was 9.4 mo (95% CI, 6.7-11.6) for pembro and 3.8 mo (95% CI, 2.9-4.3) for ipilimumab (HR, 0.64 [95% CI, 0.54-0.75]). Median modified PFS from start of second course in pts who received second-course pembro (n = 16) was 51.8 mo (95% CI, 11.0-NR); 6-year modified PFS rate was 49.2%.

Conclusions

With 10 years of follow-up, pembro continued to show improved OS vs ipilimumab. Antitumor activity was also observed in some pts who received second-course pembro. These results confirm that pembro provides long-term benefit for advanced melanoma, supporting it as a standard of care in this setting.

Clinical trial identification

NCT01866319.

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Jemimah Walker, PhD, and Mehak Aggarwal, PhD, of ApotheCom (Yardley, PA, USA).

Legal entity responsible for the study

Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Funding

Funding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA.

Disclosure

C. Robert: Financial Interests, Personal and Institutional, Advisory Board: Novartis, BMS, Roche, MSD, Sun pharma, Pierre Fabre. M.S. Carlino: Financial Interests, Personal, Advisory Board, Consultant Advisor: MSD, BMS, Novartis, Amgen, Oncosec, Merck, Sanofi, Ideaya, Pierre-Fabre, Eisai, Nektar, Regeneron. C. McNeil: Non-Financial Interests, Institutional, Principal Investigator: Merck. A. Ribas: Financial Interests, Personal, Advisory Board, Honoraria for consulting: Amgen, AstraZeneca, Merck; Financial Interests, Personal, Advisory Board, Member of the Scientific Advisory Board: Apricity, Appia, Arcus, Compugen, Immpact, Lutris, MapKure, Merus, Synthekine, Tango; Financial Interests, Personal, Member of Board of Directors, Member of the Board of Directors: Arcus, Lutris; Financial Interests, Personal, Stocks/Shares, Stock ownership: 4C Biomed, Apricity, Appia, Arcus, Compugen, Highlight, ImaginAb, Immpact, Immunesensor, Inspirna, Isoplexis, Lutris, MapKure, Merus, Pluto, Synthekine, PACT Pharma, Tango, Advaxis, CytomX, RAPT, Kite-Gilead; Financial Interests, Personal, Advisory Board: Arsenal Bio; Financial Interests, Institutional, Funding: Agilent, Bristol Myers Squibb; Non-Financial Interests, Advisory Role, Member of the scientific advisory board: Highlight, Immunesensor, Inspirna, Pluto. M.S. Nyakas: Financial Interests, Personal, Invited Speaker: Merck, BMS; Financial Interests, Personal, Principal Investigator: Merck, BMS; Other, Institutional, Principal Investigator: Lytixbiopharma, Ultimovax. D. Kee: Financial Interests, Personal, Advisory Board: Bristol Myer Squibb, Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board, Tebentafusp advisory board: Medison Pharma; Non-Financial Interests, Member: ASCO, COSA. T.M. Petrella: Financial Interests, Personal, Speaker, Consultant, Advisor: Merck, BMS, Pfizer, Sanofi, SunPharma, Novartis; Financial Interests, Personal, Other, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Sanofi, Pfizer, Novartis. M. Lotem: Other, Institutional, Invited Speaker: Merck, BMS. A.M. Arance: Financial Interests, Personal, Advisory Board, Advisory/ Speaker / Travel Expenses: Pierre Fabre, Novartis, BMS, MSD; Financial Interests, Personal, Advisory Board, Advisory: Roche; Financial Interests, Personal, Advisory Board, Advisory Role: Biontech, Almirall; Financial Interests, Institutional, Other, Research Funding: Novartis, MSD, BMS, Roche, Amgen; Financial Interests, Institutional, Funding, Research Funding: Biontech, Replimune. A. Daud: Financial Interests, Personal, Advisory Board: Merck. O. Hamid: Financial Interests, Personal, Advisory Board: Alkermes, Amgen, BMS, Bactonix, BeiGene, Bioatla, Eisai, GSK, Georgiamune, GigaGen, Grit Bio, IO Biotech, Idera, Immunocore, Incyte, Instil Bio, Iovance, Janssen, KSQ, Merck, Novartis, Obsidian, Pfizer, Roche Genentech, Seagen, Sanofi / Regeneron, Tempus, Vial, Zelluna; Financial Interests, Personal, Invited Speaker: BMS, Immunocore, Novartis, Pfizer, Sanofi / Regeneron; Financial Interests, Personal, Stocks/Shares: Bactonix; Financial Interests, Institutional, Local PI: Aduro, Akeso, Amgen, Arcus, BMS, Bioatla, CytomX, Exelixis, GSK, Idera, Immunocore, Incyte, Iovance, Merck, Merck Serono, Moderna, Nextcure, Novartis, Pfizer, Roche Genentech, Seagen, Sanofi / Regeneron, Torque, Zelluna. 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, Inselgruppe, Agence Unik; Financial Interests, Personal, Other, Consultancy: Incyte, iOnctura, Apple Tree, Merck, BMS, Eisai, Debipharm; Financial Interests, Personal, Other, Honorarium: touchIME, touchEXPERTS, VJOncology, Cambridge Healthcare Research, Royal College of Physicians; Financial Interests, Institutional, Funding: BMS, MSD, Novartis, Pfizer, Achilles, Roche, Nektar, Covance, Immunocore, Pharmacyclics, Aveo. L. Yao: Financial Interests, Personal, Full or part-time Employment, United States: Merck & Co., Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co., Inc.. R. Singh: Financial Interests, Personal, Full or part-time Employment, United States: Merck; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. R. Lal: Financial Interests, Personal, Full or part-time Employment, United States: Merck; Financial Interests, Personal, Stocks/Shares: Merck & Co., Inc.. G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L., IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V.; Financial Interests, Personal, Advisory Board, Consultant Advisor: GI Innovation; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. All other authors have declared no conflicts of interest.