855P - Safety and efficacy of vibostolimab (anti-TIGIT) coformulated with pembrolizumab (vibo/pembro) in previously untreated advanced head and neck squamous cell carcinoma (HNSCC): Results from the phase II KEYVIBE-005 study

Background

In KEYNOTE-048, patients (pts) with recurrent or metastatic HNSCC and known PD-L1 status had a statistically significant improvement in OS with pembro monotherapy vs cetuximab + chemotherapy (known as the EXTREME regimen) in the PD-L1 combined positive score (CPS) ≥1 population (median, 12.3 vs 10.4 months; HR, 0.74; 95% CI, 0.61-0.89; P = 0.00080); a favorable safety profile was observed with pembro monotherapy. TIGIT is highly coexpressed with PD-L1 in HNSCC, thus dual blockade of TIGIT and PD-1 may improve upon the efficacy observed with pembro monotherapy. Here, we present data from cohort C of the open-label phase II KEYVIBE-005 study (NCT05007106), which evaluated coformulated vibo/pembro in pts with advanced HNSCC with PD-L1 CPS ≥1.

Methods

Eligible pts had locally recurrent unresectable or metastatic HNSCC with PD-L1 CPS ≥1, an ECOG PS of 0 or 1, and no prior systemic therapy. Pts received vibo 200 mg/pembro 200 mg IV every 3 weeks for ≤35 cycles. The primary end point was ORR per RECIST v1.1 by investigator review. Secondary end points were DOR, PFS, OS, and safety.

Results

A total of 42 pts were enrolled. Median age was 62.0 years, and most pts were male (86%), had an ECOG PS of 1 (83%), and had metastatic disease (69%); 40% had tumors with PD-L1 CPS ≥20. At the data cutoff (Oct 24, 2023), median follow-up duration was 18.4 months (range, 7.9-22.3). Efficacy is presented in the Table. Treatment-related adverse events (TRAEs) occurred in 35 pts (83%); the most common (≥15%) were pruritus (31%), hypothyroidism (19%), and asthenia (17%). Grade 3 TRAEs occurred in 6 pts (14%); no grade 4 or 5 events occurred. Immune-mediated AEs and infusion reactions occurred in 13 pts (31%); 1 (2.4%) was grade 3 and none were grade 4 or 5. Table: 855P

Efficacy outcomes

aOne patient was missing a PD-L1 CPS assessment at database cutoff but was later confirmed to have PD-L1 CPS ≥1.

Conclusions

Antitumor activity was observed with vibo/pembro in pts with HNSCC with PD-L1 CPS ≥1; no new safety signals were observed.

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. Toullec: Financial Interests, Personal, Invited Speaker: Amgen, BMS, MSD, Pierre Fabre, Viatris; Financial Interests, Personal, Advisory Board: Bayer, Merck Serono, Sanofi, Servier, AstraZeneca, Oncoscience. 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. 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, 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. S. Aksoy: Financial Interests, Personal, Advisory Board: AstraZeneca, Eli Lilly, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Bristol Myers Squibb, Roche, Daiichi Sankyo: DS TR, Menarini Türkiye, Astellas Pharma, Eczacıbaşı; Financial Interests, Personal, Invited Speaker: AstraZeneca, Merck, Merck Sharp & Dohme, Novartis, Pfizer, Bristol Myers Squibb, Roche, Astellas Pharma, Eczacıbaşı, Pierre Fabre, Baxter. S. Ochsenreither: Financial Interests, Personal, Advisory Board: MSD, BMS, Janssen, Ipsen, Immunocore, Genemab, Pfizer, Pfizer; Financial Interests, Personal, Invited Speaker: MSD, Merck, Immunocore, Janssen; Financial Interests, Personal, Other, Support for travel / meeting: Janssen, Pfizer; Financial Interests, Personal, Other, Support for Travel / meeting: Merck; Financial Interests, Personal, Advisory Board, Patent of T-cell therapy target: Fred Hutchinson cancer Research Center; Financial Interests, Personal and Institutional, Research Grant: Bayer. S.Y. Rha: Financial Interests, Personal, Advisory Board: Indivumed, Amgen, LG biochemical, Astellas, Boehringer 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, Drug 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. 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: Medison; Financial Interests, Institutional, Research Grant: MSD; Financial Interests, Steering Committee Member: AstraZeneca; Financial Interests, Personal, Steering Committee Member: MSD, VBL therapeutics. Q. Liu: Financial Interests, Personal, Full or part-time Employment: Merck &Co, Inc.; Financial Interests, Personal, Stocks or ownership: Merck &Co, Inc. M. Du Plessis: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc. T. Keenan: Financial Interests, Personal, Full or part-time Employment: Merck & Co, Inc.; Financial Interests, Personal, Stocks or ownership: Merck & Co, Inc. C. Hsu: Financial Interests, Personal and Institutional, Advisory Board: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Roche; Financial Interests, Personal and Institutional, Research Grant: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Merck Sharp & Dohme, Roche; Financial Interests, Personal and Institutional, Principal Investigator: AstraZeneca, Bristol Myers Squibb, Ono Pharmaceutical, Daiichi Sankyo, Merck Sharp & Dohme, Roche; Financial Interests, Personal and Institutional, Invited Speaker: Merck Sharp & Dohme, Roche; Financial Interests, Personal, Invited Speaker: Eisai; Financial Interests, Personal and Institutional, Other, 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: BeiGene, NGM Biopharmaceuticals, Surface Oncology, Ipsen, Taiho Pharmaceuticals, TransThera Sciences. All other authors have declared no conflicts of interest.