117TiP - BGB-HNSCC-201 (NCT05909904): Phase 2, Open-Label, Multi-Arm, Global Study of Tislelizumab (TIS) + Investigational Agents as First-Line (1L) Treatment in Patients (Pts) With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma (R/M HNSCC)

Background

HNSCC is the 7^th most common cancer worldwide (Sung et al, CA Cancer J Clin 2021;71:209–249). Anti-programmed cell death-protein 1 (PD-1) therapy, either alone or in combination with chemotherapy (CT), extended overall survival (OS) vs cetuximab + CT in pts with programmed cell death-ligand 1 (PD-L1)-positive R/M HNSCC in the 1L setting; however, not all pts respond to single-agent anti-PD-1 therapy. Identifying novel agents that synergize with anti-PD-1 therapies by targeting distinct biological pathways may improve efficacy. TIS is an anti-PD-1 monoclonal antibody (mAb) currently approved in China for multiple indications. This Phase 2 study will assess efficacy and safety of TIS in combination with investigational agents targeting the immune-checkpoint inhibitors TIM-3 (BGB-A425) and/or LAG-3 (LBL-007) as 1L treatment in pts with R/M HNSCC.

Trial Design

This multicenter (77 sites; 14 countries) study will enroll approximately 160 pts (40 per arm) aged ≥18 years with immunotherapy-naïve, PD-L1 positive (combined positive score [CPS] ≥1) R/M HNSCC of the oropharynx, oral cavity, hypopharynx, or larynx, who are not candidates for local/curative therapy and have ≥1 measurable lesion (per RECIST v 1.1). Pts will be randomized 1:1:1:1 (stratified by PD-L1 CPS: 1–19 vs ≥20) to TIS monotherapy, TIS + BGB-A425, TIS + LBL-007, or TIS + BGB-A425 + LBL-007. TIS 200 mg, BGB-A425, and LBL-007will be administered by separate intravenous infusions once every 3 weeks for up to 2 years, until disease progression, intolerable toxicity, withdrawal of informed consent, or other discontinuation event, whichever occurs first. The primary endpoint is confirmed objective response rate (per investigator; RECIST v1.1). Secondary endpoints include progression-free survival, duration of response, clinical benefit rate, and disease control rate (all per investigator; RECIST v1.1) as well as safety, OS, and immunogenicity to study drugs. Enrollment is ongoing and additional experimental arms may be added in the future.

Editorial acknowledgement

Medical writing support, under the direction of the authors, was provided by Smitha Reddy, PhD, of Envision Pharma Group, and was funded by BeiGene.

Legal entity responsible for the study

BeiGene, Ltd.

Funding

BeiGene, Ltd.

Disclosure

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, Personal, Leadership Role, Chair of Steering Committee: ART NET; Non-Financial Interests, Personal, Other, Member of Global Steering Committee: MR - Linac. Y. Guo: Financial Interests, Personal, Invited Speaker: Merck Serono, Roche, MSD, BMS, BeiGene. R. Haddad: Financial Interests, Personal, Advisory Board: BMS, Merck, EMD Serono, Boehringer Ingelheim, Eisai, Bayer, Merus, AstraZeneca, Genentech, Pfizer, Genmab, Exelexis, Coherus; Financial Interests, Personal, Other, Data Safety Monitoring Board ( DSMB): Nanobiotix, PSI, Hookipa; Financial Interests, Personal, Royalties: up to date; Financial Interests, Institutional, Local PI, Grant to Hospital For Clinical Trials: Merck BMS, EMD , AstraZeneca, Incyte, Kura; Non-Financial Interests, Personal, Other, panel chair guidelines: Nccn. H.R. Kim: Financial Interests, Personal, Speaker, Consultant, Advisor, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: AstraZeneca, Bristol Myers Squibb, Genentech/Roche, MSD. C.A. Perez: Financial Interests, Personal, Advisory Board: EMD Serono; Financial Interests, Personal, Other, Steering Committee: Kinnate Biopharma Inc.; Financial Interests, Institutional, Local PI: Accutar Biotech, Kinnate Biopharma, Relay Therapeutics, Seagen Inc, Kura Oncology, Hyamab Inc, Xilio Therapeutics, Elucida Oncology, Tallac Therapeutics, Ribbon Therapeutics, Mirati Therpeutics, Elpiscience Biopharmaceuticals, Dracen Pharmaceuticals, Zhuhai Yufan Biotechnologies Co., Genentech, Inc., Jazz Pharmaceuticals, Artios Pharma, Ayala Pharmaceuticals, Elevation Oncology. I. Xiang, H. Li, G. Dong: Financial Interests, Personal, Full or part-time Employment: BeiGene. C. Even: Financial Interests, Personal, Advisory Board: BMS, MSD, Innate Pharma, Merck Serono; Financial Interests, Institutional, Advisory Board: F Star Therapeutics, Novartis, Elevar; Financial Interests, Institutional, Local PI: BMS, AstraZeneca, ISA Pharmaceutics, MSD, Debiopharma, Ayala, Gilead; Financial Interests, Institutional, Coordinating PI: BMS, Novartis, Sanofi. L.D. Locati: Financial Interests, Personal, Funding, Consulting Fees: Merck, MSD, Eisai, Bayer, Roche, Ipsen, Sanofi; Sunpharma; New Bridge; Gentili SrL; Financial Interests, Personal, Funding, Payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events: Lilly; MSD; Esiai; Financial Interests, Personal, Funding, Support for attending meetings and/or travel: Lilly; MSD; Financial Interests, Personal, Funding, Grants or contracts: MSD; Financial Interests, Personal, Advisory Board: Lilly, Bayer. All other authors have declared no conflicts of interest.