LBA36 - Nivolumab (N) + ipilimumab (I) vs EXTREME as first-line (1L) treatment (tx) for recurrent/metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Final results of CheckMate 651

Background

Despite recent tx advances in R/M SCCHN, durable survival benefit remains an elusive goal. CheckMate 651 (NCT02741570), a phase 3 randomized trial, evaluated N+I vs EXTREME regimen as 1L tx for platinum-eligible R/M SCCHN.

Methods

Pts with R/M SCCHN, no prior systemic therapy in R/M setting, and ECOG PS 0–1 were randomized 1:1 to N (3 mg/kg Q2W) + I (1 mg/kg Q6W; n = 472), or EXTREME (n = 475), stratified by tumor PD-L1 level, p16 expression, and prior chemotherapy. Pts were treated with N+I or EXTREME (cetuximab + cisplatin/carboplatin + fluorouracil ≤6 cycles, then cetuximab maintenance) until progression/unacceptable toxicity, or 2 y for N+I. Primary endpoints were overall survival (OS) in all randomized and PD-L1 combined positive score (CPS) ≥20 populations. OS in CPS ≥1 was a key secondary endpoint. Progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), and safety were also assessed.

Results

947 pts were randomized; baseline characteristics were balanced across arms. At final analysis (minimum follow-up: 27.3 mo), there was no statistically significant improvement in OS with N+I vs EXTREME in all randomized (HR 0.95 [97.9% CI: 0.80–1.13] P = 0.4951) or CPS ≥20 (HR 0.78 [97.5% CI: 0.59–1.03] P = 0.0469) populations. In pts with CPS ≥1, OS HR was 0.82 (95% CI: 0.69–0.97). Other efficacy results are in the table. Overall, 8% (N+I) and 46% (EXTREME) of pts received subsequent immunotherapy. Grade 3/4 tx-related adverse events occurred in 28% vs 71% of treated pts, respectively.

Conclusions

N+I did not show statistically significant OS improvement vs EXTREME in pts with R/M SCCHN; however, there was evidence of clinical activity in pts with CPS ≥20 and CPS ≥1 as shown by prolonged OS (median and 2 y rates) and durable responses. Notably, OS in the control arm was better than historical data. N+I had a favorable safety profile vs EXTREME, with no new safety signals observed. Table: LBA36

Clinical trial identification

NCT02741570.

Editorial acknowledgement

Writing and editorial assistance was provided by Brooke Middlebrook, CMPP, of Evidence Scientific Solutions, funded by Bristol Myers Squibb.

Legal entity responsible for the study

Bristol Myers Squibb and Ono Pharmaceutical Company Ltd.

Funding

Bristol Myers Squibb (all study sites) and Ono Pharmaceuticals (study sites in Japan, Korea and Taiwan).

Disclosure

A. Argiris: Financial Interests, Personal, Other, Review Committee: AstraZeneca; Financial Interests, Personal, Funding: BMS; Financial Interests, Personal, Invited Speaker: BMS; Financial Interests, Personal, Other, Review Committee: Debiopharm; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc.; Financial Interests, Personal, Funding: Rakuten Medical, Inc. K. Harrington: Financial Interests, Institutional, Advisory Board: Arch Oncology; Financial Interests, Institutional, Advisory Board: AstraZeneca; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Advisory Board: BMS; Financial Interests, Institutional, Invited Speaker: BMS; Financial Interests, Institutional, Advisory Board: Boehringer-Ingelheim; Financial Interests, Institutional, Research Grant: Boehringer-Ingelheim; Financial Interests, Institutional, Advisory Board: Codiak; Financial Interests, Institutional, Advisory Board: Inzen; Financial Interests, Institutional, Advisory Board: Merck-Serono; Financial Interests, Institutional, Invited Speaker: Merck-Serono; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Institutional, Advisory Board: Oncolys; Financial Interests, Institutional, Advisory Board: Pfizer; Financial Interests, Institutional, Advisory Board: PsiVac; Financial Interests, Institutional, Advisory Board: Replimune; Financial Interests, Institutional, Research Grant: Replimune. M. Tahara: Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Advisory Board: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Research Grant: Ono Pharmaceutical; Financial Interests, Personal and Institutional, Invited Speaker: BMS; Financial Interests, Personal and Institutional, Advisory Board: BMS; Financial Interests, Personal and Institutional, Research Grant: BMS; Financial Interests, Personal and Institutional, Invited Speaker: MSD; Financial Interests, Personal and Institutional, Advisory Board: MSD; Financial Interests, Personal and Institutional, Research Grant: MSD; Financial Interests, Personal and Institutional, Invited Speaker: Bayer; Financial Interests, Personal and Institutional, Advisory Board: Bayer; Financial Interests, Personal and Institutional, Research Grant: Bayer; Financial Interests, Personal and Institutional, Invited Speaker: Merck Biopharma; Financial Interests, Personal and Institutional, Advisory Board: Merck Biopharma; Financial Interests, Personal and Institutional, Research Grant: Merck Biopharma; Financial Interests, Personal and Institutional, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Advisory Board: Eisai; Financial Interests, Personal and Institutional, Research Grant: Eisai; Financial Interests, Personal, Advisory Board: LOXO; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal and Institutional, Invited Speaker: Rakuten Medical; Financial Interests, Personal and Institutional, Advisory Board: Rakuten Medical; Financial Interests, Personal and Institutional, Research Grant: Rakuten Medical; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal and Institutional, Advisory Board: Novartis; Financial Interests, Personal and Institutional, Research Grant: Novartis. R.L. Ferris: Financial Interests, Personal, Advisory Board: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Aduro Biotech, Inc; Financial Interests, Institutional, Funding: AstraZeneca/MedImmune; Financial Interests, Personal, Advisory Role: Bicara Therapeutics, Inc; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Advisory Role: Everest Clinical Research Corporation; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd; Financial Interests, Personal, Advisory Role: Genocea Biosciences, Inc; Financial Interests, Personal, Advisory Board: Instil Bio, Inc; Financial Interests, Personal, Advisory Role: Kowa Research Institute, Inc.; Financial Interests, Personal, Advisory Board: Lifescience Dynamics Limited; Financial Interests, Personal, Advisory Board: MacroGenics, Inc.; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Role: Mirati Therapeutics, Inc; Financial Interests, Personal, Advisory Role: Nanobiotix; Financial Interests, Personal, Advisory Role: Novasenta; Financial Interests, Personal, Stocks/Shares: Novasenta; Financial Interests, Institutional, Funding: Novasenta; Financial Interests, Personal, Advisory Board: Numab Therapeutics AG; Financial Interests, Personal, Advisory Board: OncoCyte Corporation; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Role: PPD; Financial Interests, Personal, Advisory Board: Rakuten Medical, Inc; Financial Interests, Personal, Advisory Role: Sanofi; Financial Interests, Personal, Advisory Board: Seagen, Inc; Financial Interests, Institutional, Funding: Tesaro; Financial Interests, Personal, Advisory Role: Zymeworks, Inc. M. Gillison: Financial Interests, Personal and Institutional, Advisory Role: Istari Oncology Inc; Financial Interests, Personal and Institutional, Advisory Role: LLX Solutions, LLC; Financial Interests, Personal and Institutional, Advisory Role: Kura Oncology; Financial Interests, Personal and Institutional, Advisory Role: Mirati Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: BioNtech AG; Financial Interests, Personal and Institutional, Advisory Role: Shattuck Labs, Inc; Financial Interests, Personal and Institutional, Advisory Role: EMD Serono, Inc; Financial Interests, Personal and Institutional, Advisory Role: Depiopharm; Financial Interests, Personal and Institutional, Advisory Role: Merck & Co; Financial Interests, Personal and Institutional, Advisory Role: Ipsen Biopharmaceuticals Inc; Financial Interests, Personal and Institutional, Advisory Role: Gilead Sciences, Inc; Financial Interests, Personal and Institutional, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Advisory Role: Bicara Therapeutics; Financial Interests, Personal and Institutional, Advisory Role: Bayer Healthcare Pharmaceutics; Financial Interests, Personal and Institutional, Advisory Role: Genocea Biosciences, Inc.; Financial Interests, Personal and Institutional, Invited Speaker: OncLive; Financial Interests, Personal and Institutional, Invited Speaker: Roche; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Seagen; Financial Interests, Personal and Institutional, Advisory Role, Scientific advisory committee: Sensei Biotherapeutics, Inc; Financial Interests, Personal and Institutional, Funding, Research funding: Genocea Biosciences, Inc; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Genentech; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Kura; Financial Interests, Personal and Institutional, Invited Speaker, Research funding: Cullinan Labs; Financial Interests, Personal and Institutional, Other, DSBM: SQZBiotech; Financial Interests, Personal and Institutional, Other, DSBM: BioMimetix. J. Fayette: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Advisory Board: BMS; Financial Interests, Personal, Advisory Board: Innate Pharma,; Financial Interests, Personal, Advisory Board: Merck Serono,; Financial Interests, Personal, Advisory Board: MSD; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Institutional, Other, Research Funding: Seagens; Non-Financial Interests, Personal, Principal Investigator: AstraZeneca . A. Daste: Financial Interests, Personal, Advisory Role, Consulting: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role, Consulting: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Role, Consulting: Merck. R. Mesia Nin: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Nanobiotics; Financial Interests, Personal, Advisory Board: Seattle Genetics; Financial Interests, Personal, Advisory Board: Boeringer Ingelheim. N.F. Saba: Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board: Kura; Financial Interests, Personal, Advisory Board: CUE; Financial Interests, Institutional, Funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding: Exelixis; Financial Interests, Personal, Advisory Role: Pfizer . M. Mak: Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Invited Speaker: Takeda; Financial Interests, Personal, Invited Speaker: Amgen. M.A. Álvarez Avitia: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: Janssen Mexico; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Ipsen. A. Guminski: Financial Interests, Personal, Advisory Board: BMS; Non-Financial Interests, Personal, Other, Conference Travel Support: BMS; Financial Interests, Personal, Advisory Board: Regeneron; Non-Financial Interests, Personal, Principal Investigator: Regeneron; Financial Interests, Personal, Advisory Board: Sanofi; Financial Interests, Personal, Advisory Board: Merck KgA; Non-Financial Interests, Personal, Other, Conference Travel Support: Merck KgA; Non-Financial Interests, Personal and Institutional, Principal Investigator, Investigator Initiated Trial Support: AstraZeneca; Financial Interests, Personal, Advisory Board: MSD; Non-Financial Interests, Personal and Institutional, Research Grant: Sun Pharma; Financial Interests, Personal, Advisory Board: Sun Pharma. U. Müller-Richter: Non-Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Non-Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Non-Financial Interests, Institutional, Funding: Bristol Myers Squibb; Non-Financial Interests, Institutional, Principal Investigator: Bristol Myers Squibb; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Invited Speaker: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Expert Testimony: Merck, Sharp & Dohme; Non-Financial Interests, Institutional, Funding: Merck, Sharp & Dohme; Financial Interests, Institutional, Principal Investigator: Merck, Sharp & Dohme; Non-Financial Interests, Personal, Advisory Board: Sanofi; Non-Financial Interests, Personal, Expert Testimony: Sanofi; Non-Financial Interests, Personal, Writing Engagements: Sanofi; Non-Financial Interests, Institutional, Funding: KuraOncology; Non-Financial Interests, Institutional, Principal Investigator: KuraOncology; Non-Financial Interests, Institutional, Funding: AstraZeneca; Non-Financial Interests, Institutional, Principal Investigator: AstraZeneca; Non-Financial Interests, Institutional, Funding: BioNTech; Non-Financial Interests, Institutional, Principal Investigator: BioNTech. N. Kiyota: Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bayer; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Eisai; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: ONO; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Bristol Myers Squibb; Financial Interests, Personal, Speaker’s Bureau, Speaker of sponsored seminar: Merck, Sharp & Dohme; Financial Interests, Institutional, Research Grant: Adlai Nortye; Financial Interests, Institutional, Research Grant: Bayer; Financial Interests, Institutional, Research Grant: ONO; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Institutional, Research Grant: Rakuten Medical; Financial Interests, Institutional, Advisory Role: Adlai Nortye; Financial Interests, Institutional, Advisory Role: ONO. M. Roberts: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS . T.A. Khan: Financial Interests, Personal, Full or part-time Employment: BMS; Financial Interests, Personal, Stocks/Shares: BMS. K. Miller-Moslin: Financial Interests, Personal, Full or part-time Employment: Bristol Myers Squibb. L. Wei: Financial Interests, Personal, Full or part-time Employment: BMS. R. Robert Haddad: Financial Interests, Personal, Full or part-time Employment: Dana-Farber Cancer Institute; Financial Interests, Personal, Leadership Role: National Comprehensive Cancer Network; Financial Interests, Personal, Advisory Role: Celgene; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Pfizer; Financial Interests, Personal, Advisory Role: Loxo; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Immunomic Therapeutics; Financial Interests, Personal, Advisory Role: GSK; Financial Interests, Personal, Advisory Role: Gilead Sciences; Financial Interests, Personal, Advisory Role: Vaccinex; Financial Interests, Personal, Advisory Role: EMD Serono; Financial Interests, Personal, Advisory Role: BioNTech AG; Financial Interests, Personal, Advisory Role: Achilles Therapeutics; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Institutional, Funding, Research Funding: Boehringer Ingelheim; Financial Interests, Institutional, Funding, Research Funding: Merck; Financial Interests, Institutional, Funding, Research funding: Bristol Myers Squibb; Financial Interests, Institutional, Funding, Research funding: Celgene; Financial Interests, Institutional, Funding, Research funding: AstraZeneca; Financial Interests, Institutional, Funding, Research Funding: VentiRx; Financial Interests, Institutional, Funding, Research Funding: Genentech; Financial Interests, Institutional, Funding, Research Funding: Pfizer; Financial Interests, Institutional, Funding, Research Funding: Kura; Financial Interests, Personal, Other: Nanobiotix; Financial Interests, Personal, Other: ISA Pharmaceuticals; Financial Interests, Personal, Other, Patents, Royalties, Other Intellectual Property: UpToDate. All other authors have declared no conflicts of interest.