908P - Association of biomarkers with response to first-line (1L) vibostolimab (anti-TIGIT) coformulated with pembrolizumab (vibo/pembro) in advanced head and neck squamous cell carcinoma (HNSCC): Results from KEYVIBE-005

Background

In cohort C of the multicohort phase II KEYVIBE-005 study (NCT05007106), 1L vibo/pembro showed an ORR of 29% and a manageable safety profile in 42 patients (pts) with recurrent or metastatic HNSCC with PD-L1 CPS ≥1. The association between exploratory biomarkers and response was evaluated.

Methods

Using tumor samples, expression of TIGIT on immune cells (ICs) and PD-L1 CPS were evaluated by IHC; 17-gene T-cell–inflamed gene expression profile (Tcell_infGEP) and poliovirus receptor (PVR) by RNA sequencing; and TMB by WES. Circulating tumor DNA (ctDNA) was isolated from predose plasma samples collected on day 1 of cycle 1 (C1), C2, and C3 and sequenced using a personalized tumor-informed assay; quantity was expressed as maximum somatic allele frequency (MSAF). Change in MSAF was assessed from C1 to C2 and C3. Spearman correlation was used to assess the relationship between total ICs and the proportion of TIGIT+ ICs. Association of each biomarker (continuous) with response was evaluated using AUROC (hypothesized positive association). Data cutoff was Oct 24, 2023.

Results

TIGIT was evaluable in 38 pts, PD-L1 in 42 pts, Tcell_infGEP and PVR in 27 pts, TMB in 21 pts, and C1 ctDNA in 20 pts. Total ICs and TIGIT+ ICs were correlated (ρ = 0.82). The AUROC (95% CI) for discriminating TIGIT, PD-L1, Tcell_infGEP, and TMB as predictors of response were 0.37 (0.17-0.57), 0.63 (0.45-0.82), 0.39 (0.15-0.62), and 0.77 (0.55-0.99), respectively. No clear associations between PVR and response were observed. At C1, median ctDNA MSAF was 0.4% in responders and 4.6% in nonresponders. Larger ctDNA decreases were observed in responders with median fold changes from C1 at C2 and C3 of 0.45 and 0.55, respectively, vs 1.09 and 0.93, respectively, in nonresponders.

Conclusions

In pts with PD-L1–positive HNSCC, PD-L1 and TMB showed trends of a positive association with response to 1L vibo/pembro; TIGIT, Tcell_infGEP, and PVR did not show an association with response. Trends towards lower baseline ctDNA burden and larger on-treatment ctDNA decreases were observed in responders vs nonresponders, suggesting the utility of liquid biopsy for disease monitoring.

Clinical trial identification

NCT05007106 (2021-09-16).

Editorial acknowledgement

Medical writing and/or editorial assistance was provided by Shanel Dhani, PhD, Mehak Aggarwal, PharmD, and Holly C. Cappelli, PhD, CMPP, of ApotheCom (Yardley, PA, USA). This assistance was funded by Merck Sharp & Dohme LLC, a subsidiary of Merck & Co, Inc.

Legal entity responsible for the study

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

Funding

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

Disclosure

C. Hsu: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Roche; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Merck Sharp & Dohme, Roche; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Invited Speaker: Ono Pharmaceutical, Bristol Myers Squibb, Merck Sharp & Dohme, Roche; Financial Interests, Personal and Institutional, Principal Investigator, of a participating site of sponsor-initiate multicenter studies, and of an investigator-initiated clinical trial: Ono Pharmaceutical, Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Other, Steering committee member of a sponsor-initiated multicenter clinical trial: Daiichi Sankyo; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Principal Investigator, of a participating site of sponsor-initiate multicenter studies: Roche; Financial Interests, Personal and Institutional, Other, Include description) Steering committee member of a sponsor-initiated multicenter clinical trial: Roche; Financial Interests, Institutional, Research Grant: BeiGene, NGM Biopharmaceuticals, Surface Oncology, Ipsen, Taiho Pharmaceuticals, TransThera Sciences; Financial Interests, Institutional, Principal Investigator, of a participating site of sponsor-initiate multicenter studies, and of an investigator-initiated clinical trial: BeiGene; Financial Interests, Institutional, Principal Investigator, of a participating site of a sponsor-initiate multicenter study: NGM Biopharmaceuticals, Surface Oncology, Taiho Pharmaceuticals; Financial Interests, Institutional, Principal Investigator, on an investigator-initiated clinical trial: Ipsen; Financial Interests, Institutional, Principal Investigator, of a participating site of a sponsor-initiated multicenter study: TransThera Sciences. F. Ghiringhelli: Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Amgen, merck serono, MSD. C.I. Rojas: Financial Interests, Personal, Advisory Board: BMS, Roche, Roche, MSD, Pfizer, Sanofi; Financial Interests, Personal, Invited Speaker: BMS, MSD, AstraZeneca, Knight, Pfizer; Financial Interests, Personal, Member of Board of Directors: Bradford Hill. M.A.N. Sendur: Financial Interests, Personal, Advisory Board: BMS, Pfizer, Takeda, Roche, astellas; Financial Interests, Personal, Invited Speaker: Astellas, Pfizer, BMS, MSD, roche. C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene, ALX Oncology, Exscientia. R. Shapira-Frommer: Financial Interests, Personal, Advisory Board: MSD, Neopharm; Financial Interests, Personal, Invited Speaker: MSD, BMS, AstraZeneca, Medison, Novartis, Roche; Financial Interests, Personal, Other, consultation: Msdison; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Steering Committee Member: AstraZeneca; Financial Interests, Personal, Steering Committee Member: MSD, VBL therapeutics. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, beringer Ingelheim; Financial Interests, Personal, Invited Speaker: MSD, Daiichi Sankyo; Financial Interests, Personal, Steering Committee Member: Amgen; Financial Interests, Institutional, Funding: MSD, Lilly; Financial Interests, Institutional, Research Grant: BMS, Daiichi Sankyo; Financial Interests, Institutional, Local PI: Indivumed, AstraZeneca; Financial Interests, Other, Durg supply for clinical trial: Merck; Financial Interests, Institutional, Coordinating PI, Drug supply for clincal trial: MSD; Financial Interests, Institutional, Local PI, drug supply for clinical trial: zy,meworks; Financial Interests, Institutional, Local PI, drug supply for clincial trial: Beigine; Financial Interests, Local PI: Roche. Y. Zhang: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co, Inc.; Non-Financial Interests, Personal, Proprietary Information: Merck & Co, Inc. C. Chen: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks/Shares: Merck & Co, Inc. C.E. Pena, T. Keenan: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co, Inc. Y. Chen: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks or ownership: GSK, Adaptimmune; Financial Interests, Personal, Proprietary Information: GSK. E. Dettman: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co, Inc. A.G. Robinson: Financial Interests, Personal and Institutional, Advisory Board: Merck Sharp Dohme, Eisai, AstraZeneca, Bristol Myers Squibb; Financial Interests, Personal and Institutional, Sponsor/Funding: Merck Sharp Dohme, Eisai, AstraZeneca, Bristol Myers Squibb. All other authors have declared no conflicts of interest.