28P - 3-year follow-up analysis of disease-free survival in CheckMate 274 by PD-L1 expression using tumor cell and combined positive scoring algorithms

Background

CheckMate 274 met the primary endpoints of improved disease-free survival (DFS) with nivolumab (NIVO) v placebo (PBO) both in the intent-to-treat (ITT) population and in patients (pts) with programmed death-ligand 1 (PD-L1) expression ≥1% assessed by tumor cell score (TC). We report updated analysis of DFS by PD-L1 expression as assessed by both TC and combined positive score (CPS; measuring PD-L1 on both tumor and immune cells) with minimum follow-up in the ITT population of 31.6 months.

Methods

CheckMate 274 (NCT02632409) is a phase 3, randomized, double-blind, trial of adjuvant NIVO v PBO in pts with muscle-invasive urothelial carcinoma who are at high risk of recurrence after radical resection. Pts were randomized 1:1 to NIVO 240mg or PBO every 2 weeks intravenously for ≤1 year. Primary endpoints are DFS in the ITT population and in pts with TC PD-L1≥1%. CPS was determined retrospectively from the previously stained immunohistochemistry slides. This analysis only included pts with PD-L1 quantifiable by both CPS and TC.

Results

630 pts had quantifiable PD-L1 by TC and CPS; 250 (40%) had TC≥1% (NIVO, n=125; PBO, n=125), 380 (60%) had TC<1% (NIVO, n=191; PBO, n=189), 558 (89%) had CPS≥1 (NIVO, n=282; PBO, n=276), and 72 (11%) had CPS<1 (NIVO, n=34; PBO, n=38). In pts with TC<1%, 81% (n=309) had CPS≥1. Table shows the number of pts and DFS outcomes in pts with TC≥1% and CPS≥1. In pts with TC<1% who also had CPS≥1, median DFS (95% CI) was 19.2 (16.1-25.6) months with NIVO vs. 10.4 (8.2-19.4) months with PBO; HR for NIVO v PBO in these pts was 0.79 (95% CI, 0.60-1.05). Table: 28P

HR, hazard ratio; mo, months; NE, not estimable.

Conclusions

With extended follow-up, this exploratory analysis of PD-L1 expression by CPS showed that most pts with TC<1% had CPS ≥1. In pts with TC<1% and CPS≥1, median DFS with NIVO was nearly double that with PBO. These results support the interpretation that most pts with TC<1% also benefit from adjuvant NIVO.

Clinical trial identification

CheckMate 274 (NCT02632409).

Legal entity responsible for the study

BMS.

Funding

BMS.

Disclosure

F. Stenner-Liewen: Consulting or Advisoy role: BMS/Roche, Ipsen, MSD, Novartis, Pfizer. Research funding: BMS GmbH & Co. KG, Takeda. Travel, accommodations, expenses: BMS GmbH & Co. KG, Roche. M. Galsky: Consulting or Advisoy role: Biomotiv, Janssen, Dendreon, Merck, GSK, Lilly, Astellas Pharma, Genentech, BMS, Novartis, Pfizer, EMD Serono, AstaZeneca, Seagen, Incyte, Aileron Therapeutics, Dracen, Inovio Pharmaceuticals, NuMab, Dragongly Therapeutics, Basilea, UroGen Pharma, Infinity Pharmaceuticals, Gilead Sciences, Silverback Therapeutics, AbbVie; Patents, Royalties, Other Intellectual Property: Methods and compositions for treating cancer and related methods. Mount Sinai School of Medicine July 2012, Application number: 20120322792. Stock and Other Ownership Interests: Rappta Therapeutics. Research funding (my institution): AstraZeneca, Bristol Myers Squibb, Dendreon, Genentech/Roche, Janssen Oncology, Merck, Novartis. D. Bajorin: Consulting or Advisoy role: Merck, Dragonfly Therapeutics, Fidia Farmaceutici S.p.A., Bristol Myers Squibb Foundation; Travel, accommodations, expenses: Merck; Research funding (my institution): Novartis, Merck, BMS, AstraZeneca, Astellas Pharma, Seattle Genetics/Astellas. J. Witjes: Consulting or Advisoy role: Nucleix, BMS, MSD, Ipsen, Sanofi/Aventis, Janssen Oncology, Oncodiag, BeiGene, Ferring, AstraZeneca, Asieris Pharmaceuticals, Photocure; Honoraria: Astellas Pharma, BeiGene, Ferring, AstraZeneca, Janssen, MSD, BMS/Pfizer. J. Gschwend: Consulting or Advisoy role: Janssen-Cilag, Bayer Schering Pharma, BMS; Honoraria: Janssen-Cilag, Bayer Schering Pharma, BMS. Y. Tomita: Consulting or Advisoy role: Eisai, MSD Onco Pharmaceutical, Taiho Pharmaceutical; Honoraria: Astellas Pharma, BMS Japan, Chugai Pharma, Ono Pharmaceutical, Takeda, Merck, Pfizer, MSD; Research funding (my institution): Astellas Pharma, AstraZeneca, Chugai Pharma, Eisai, MSD, Ono Pharmaceutical, Pfizer, Takeda. F. Nasroulah, M. Askelson, J.M. David: Financial Interests, Institutional, Full or part-time Employment: BMS; Stock and Other Ownership Interests: BMS. B. Perez Valderrama: Consulting or Advisoy role: BMS/Medarex, MSD Oncology, Astellas Pharma, Novartis, Bayer, Advanced Accelerator Applications/Novartis; Travel, accommodations, expenses: Merck/Pfizer; Honoraria: BMS/Medarex, Roche, EUSA Pharma, Pfizer, Astellas Pharma, Bayer, Merck/Pfizer, Merck. M-O. Grimm: Consulting or Advisoy role: AstraZeneca, BMS, Ipsen, MSD, Pfizer, EUSA Pharma, Merck Serono, Takeda, Eisai, Bayer Vital, Janssen Cilag, Gilead Sciences, Novartis; Honoraria: AstraZeneca, BMS, MSD, Pfizer, Ipsen, Merck Serono, EUSA Pharma, Janssen Cilag; Travel, accommodations, expenses: BMS, Merck Serono, MSD, Janssen Cilag, Ipsen, AstraZeneca; Research funding (my institution): BMS, Intutive Surgical, Bayer Vital. L. Appleman: Consulting or Advisoy role: AADi; Travel, accommodations, expenses: BMS, Merck Serono, MSD, Janssen Cilag, Ipsen, AstraZeneca; Other relationship: Pfizer; Research funding (my institution): Pfizer, Exelixis, BMS, Astellas Pharma, Acerta Pharma, Novartis, Bayer, Agensys, Merck, Genentech/Roche, Tokai Pharmaceuticals, AVEO, Peloton Therapeutics, Calithera Bioscences, Seattle Genetics, Inovio Pharmaceuticals, Eisai, Lilly, Amgen, Surgace Oncology, BioNTech AG. G. Gravis: Research funding (my institution): BMS; Payment or honoraria for speakers’ bureaus (institutional): Janssen Oncology, Ipsen, BMS, Amgen, Sanofi/Aventis, MSD Oncology, Astellas Pharma; Support for attending meetings and/or travel: Janssen Oncology, BMS, Astellas Pharma, Pfizer, Ipsen, Sanofi, AstraZeneca; Participation on a Data Safety Monitoring Board or Advisory Board (institutional): BMS, Janssen, Ipsen, Sanofi/Aventis, MSD Oncology, Pfizer, Bayer, AstraZeneca. A. Necchi: Consulting or Advisoy role: Merck Sharp & Dohme, Roche, Bayer, AstraZeneca, Clovis Oncology, Janssen, Incyte, Seattle Genetics/Astellas, BMS, Rainier Therapeutics, GSK, Basilea Pharmaceutical, Catalym; Travel, accommodations, expenses: Roche, Merck Sharp & Donhme, AstraZeneca, Janssen, Rainier Therapeutics, Pfizer; Employment, other relationship and stock and other ownership interest: Bayer (An Immediate Family Member); Honoraria: Roche, Merck, AstraZeneca, Janssen, Foundation Medicine, BMS, Astellas Pharma; Research funding: Ipsen, Gilead Sciences Research funding (institution): Merck Sharp & Dohme, AstraZeneca. All other authors have declared no conflicts of interest.