Abstract 907P
Background
Pembro improved OS over SOC in patients (pts) with previously treated R/M HNSCC in the phase III KEYNOTE-040 study (NCT02252042). We present the associated exploratory biomarker results including TMB, PD-L1 CPS, and T-cell–inflamed gene signature (TcellinfGEP).
Methods
Pts with HNSCC who progressed during or after platinum-containing therapy for R/M disease, or whose disease recurred or progressed within 3-6 mo of prior multimodal platinum-containing therapy were randomly assigned 1:1 to pembro 200 mg Q3W or investigator’s choice of SOC. Association of TMB by WES, PD-L1 CPS (IHC 22C3 pharmDx), and TcellinfGEP by RNAseq with clinical response (ORR [logistical regression], PFS and OS [Cox model]) was evaluated within each treatment arm. The Spearman correlation was calculated between TMB, PD-L1 CPS, and TcellinfGEP, as continuous scores. Nominal significance was prespecified at P = 0.05 (pembro, 1-sided; SOC, 2-sided).
Results
Of 495 pts, 365 (184 pembro; 181 SOC) had WES samples, 476 (245 pembro; 231 SOC) had PD-L1 CPS results, and 313 (156 pembro; 157 SOC) had samples for RNAseq. TMB, PD-L1 CPS, and TcellinfGEP were all associated with improved ORR, PFS, and OS for pembro (P < 0.05); no associations were observed for SOC (P > 0.05). Additional biomarker analyses using prespecified cutpoints are shown in the table. Within the pembro arm, TMB was weakly correlated with PD-L1 CPS (r = 0.1) or TcellinfGEP (r = 0.01); PD-L1 CPS and TcellinfGEP were moderately correlated (r = 0.49). Table: 907P
Biomarker analyses at prespecified cut points
| PFS HR (95% CI) | OS HR (95% CI) | |
| PD-L1 | ||
CPS ConclusionsIn this exploratory analysis of KEYNOTE-040, higher TMB, PD-L1 CPS, and TcellinfGEP were associated with improved outcomes for pembro in pts with R/M HNSCC, but were not prognostic for SOC. These results suggest utility of TMB, PD-L1 CPS, and TcellinfGEP in characterizing response to pembro in HNSCC and support continued research in earlier lines of therapy. Clinical trial identificationNCT02252042; release date: September 29, 2014. Editorial acknowledgementMedical writing and editorial assistance was provided by Mallory Campbell, PhD, and Robert Steger, PhD, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc, Rahway, NJ, USA. Legal entity responsible for the studyMerck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. FundingFunding for this research was provided by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc. DisclosureD. Soulieres: Financial Interests, Personal and Institutional, Advisory Board: Merck & Co, Inc, Adlai-Nortye, EMD-Serono; Financial Interests, Personal and Institutional, Research Grant: Merck & Co, Inc, Adlai-Nortye, EMD-Serono; Financial Interests, Personal and Institutional, Invited Speaker: Merck & Co, Inc, Adlai-Nortye; Financial Interests, Institutional, Research Grant: Incyte, GSK. C. Le Tourneau: Financial Interests, Personal, Advisory Board: MSD, BMS, Merck Serono, Roche, ALX Oncology, Seattle Genetics, Aveon, Immutep, Seagen, Meerus, Exscientia, MaxiVax, PCI Biotech, Nanobiotix, Onxeo. J. Machiels: Financial Interests, Institutional, Advisory Board, Travel Expenses, Research Funding: Pfizer, BMS, CureVac; Financial Interests, Institutional, Advisory Board, Research Funding: Roche, Bayer, Merck Serono, Serono, Boerhinger Ingelheim, Novartis, Incyte, Cue Biopharma, ALX Oncology, iTEOS, eTheRNA, NEKTAR, F-Star, Seagen, Genmab, Astellas, MSD, GSK, Merus; Financial Interests, Other, Travel Expenses: Amgen, Gilead, Sanofi; Financial Interests, Other, Data Safety Monitoring Board with Honoraria: Psioxus; Financial Interests, Personal, Other, Investigator and Study Coordinator: EORTC. B. Burtness: Financial Interests, Personal and Institutional, Advisory Board, Research Grant, Principal Investigator, Advisory Role: Yale School of Medicine. K.J. Harrington: Financial Interests, Institutional, Advisory Board: Amgen, AstraZeneca, BMS, Boehringer Ingelheim, Merck, MSD, Pfizer, Replimune, Oncolys, Vyriad, Idera; Financial Interests, Institutional, Other, Honoraria for lectures: Amgen, AstraZeneca, BMS, Boehringer Ingelheim; Financial Interests, Institutional, Advisory Board, Advisory board for CD47 assets: Arch Oncology; Financial Interests, Institutional, Advisory Board, Development of DDR assets: ARTIOS; Financial Interests, Institutional, Advisory Board, Development of exosomal STING agonist: Codiak; Financial Interests, Institutional, Advisory Board, Development of oncolytic adenovirus: PsiVac; Financial Interests, Institutional, Funding, Research: AstraZeneca, Boehringer Ingelheim, MSD; Financial Interests, Institutional, Funding, Development of oncolytic HSV platform: Replimune; Non-Financial Interests, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Other, Member of Global Steering Committee: MR - Linac. J. Shen, J. Tao, A. Webber, A. Vajdi: Financial Interests, Personal, Stocks/Shares: Merck & Co, Inc.; Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc. A. Loboda: Financial Interests, Personal, Full or part-time Employment: MSD. N. Lerman: Financial Interests, Personal, Stocks/Shares: Merck & Co, Inc.; Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc. B. Gumuscu: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co, Inc.; Financial Interests, Personal, Other, Travel: Merck & Co, Inc. L.F.L. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Boehringer Ingelheim, Hoffmann-La Roche Ltd, Novartis, Roche, Debiopharm International SA, Sobi, Incyte Biosciences Italy srl, Doxa Pharma srl, Amgen, Nanobiotics, GSK; Financial Interests, Institutional, Research Grant, Funds received by my institution for clinical studies and research activities in which I am involved: AstraZeneca, BMS, Boehringer Ingelheim, Celgene International, Eisai, Exelixis, Debiopharm International SA, Hoffmann-La roche ltd, IRX Therapeutics, Medpace, Merck Serono, Merck Healthcare KGaA, MSD, Novartis, Pfizer, Roche, Adlai Nortye. 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