Abstract 705TiP
Background
Anti-PD-(L)1 therapies have improved clinical outcomes in PD-L1+ squamous cell carcinoma of the head and neck (SCCHN). However, many patients either do not respond or develop resistance, partly due to additional immune checkpoint receptors including LAG-3 and TIM-3, which are frequently coexpressed with PD-1 in tumor infiltrating lymphocytes. In preclinical studies, LAG-3 and TIM-3 blockade showed synergistic activity with PD-1 inhibition, and triple blockade improves T-cell reinvigoration and antitumor efficacy over single/double combinations. Emerging clinical evidence also supports blockade of PD-1, LAG-3, and TIM-3 as a promising combination approach in checkpoint inhibitor-naive patients. This study aims to assess the efficacy and safety of the anti–PD-1 antibody retifanlimab in combination with INCAGN02385 (anti–LAG3) and INCAGN02390 (anti–TIM-3) antibodies as first-line treatment in PD-L1+ recurrent or metastatic SCCHN.
Trial design
This randomized, double-blind, multicenter, phase 2 study (NCT05287113) includes patients with previously untreated, recurrent or metastatic, PD-L1+ (combined positive score (CPS) ≥1%) SCCHN and Eastern Cooperative Oncology Group (ECOG) status of 0 or 1. Approximately 162 patients will be randomized 1:1:1 to receive (1) intravenous (IV) retifanlimab 500 mg every 4 weeks (Q4W) plus placebo controls, (2) retifanlimab plus IV INCAGN02385 350 mg Q2W plus placebo, or (3) retifanlimab plus INCAGN02385 plus IV INCAGN02390 400 mg Q2W. Patients will be stratified at randomization by LAG-3 expression (tumor proportion score ≥5% vs <5%), PD-L1 CPS (1%–19% vs ≥20%), and human papillomavirus p16 status (positive vs negative; oropharyngeal tumors only). Treatment will be administered in 4-week cycles for up to 2 years. The primary endpoint is progression-free survival (defined per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1). Secondary endpoints are objective response per RECIST v1.1, duration of response, disease control, overall survival and safety.
Clinical trial identification
NCT05287113.
Editorial acknowledgement
Writing assistance was provided by Cory Pfeiffenberger, PhD (ICON, Blue Bell, PA, USA).
Legal entity responsible for the study
Incyte Corporation.
Funding
Incyte Corporation.
Disclosure
C. Le Tourneau: Financial Interests, Personal, Advisory Board: BMS, MSD, Merck Serono, Nanobiotix, Roche, Rakuten, Seattle Genetics, GSK, Celgene. L.F. Licitra: Financial Interests, Personal, Advisory Board, for expert opinion in advisory boards: AstraZeneca, Bayer, BMS, Eisai, MSD, Merck Serono, Boehringer Ingelheim, F. 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, Buran. N. Bourayou: Financial Interests, Personal, Full or part-time Employment: Incyte. R. Schaub: Financial Interests, Institutional, Full or part-time Employment: Incyte. M. Bartenstein: Financial Interests, Personal, Full or part-time Employment: Incyte. W. Wei: Financial Interests, Personal and Institutional, Full or part-time Employment: Incyte. E.E.W. Cohen: Financial Interests, Personal, Other, Consulting: Axelia, Cel Sci, Eisai, Hoopika, ImmunoSensor, Istari, Janssen, Kahr Medical, Mana Therapeutics, Merck, Mirati, MSD, Nectin Tx, Pangea Therapeutics, Roche; Financial Interests, Personal, Other, DSMB: Ayala, Kura; Financial Interests, Personal, Stocks/Shares: Kinnate Biophama, Primmune Therapeutics.