Abstract
Phase 2 trial of retifanlimab (anti–PD-1) in combination with INCAGN02385 (anti–LAG-3) and INCAGN02390 (anti–TIM-3) as first-line treatment in patients with PD-L1–positive recurrent/metastatic squamous cell carcinoma of the head and neck.
Author
Ezra E.W. Cohen
Moores Cancer Center, University of California San Diego, La Jolla, CA
info_outline
Ezra E.W. Cohen, Christophe Le Tourneau, Richard Schaub, Matthias Bartenstein, Lulu Cheng, Lisa F. Licitra
Full text
Authors
Ezra E.W. Cohen
Moores Cancer Center, University of California San Diego, La Jolla, CA
info_outline
Ezra E.W. Cohen, Christophe Le Tourneau, Richard Schaub, Matthias Bartenstein, Lulu Cheng, Lisa F. Licitra
Organizations
Moores Cancer Center, University of California San Diego, La Jolla, CA, Institut Curie, Paris, France, Incyte Corporation, Wilmington, DE, Incyte Biosciences International Sarl, Morges, Switzerland, Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy
Abstract Disclosures
Research Funding
Pharmaceutical/Biotech Company
Incyte Corporation
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 on 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–LAG-3) and INCAGN02390 (anti–TIM-3) antibodies as first-line treatment in PD-L1+ recurrent or metastatic SCCHN.
Methods:
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 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 (PFS; defined per Response Evaluation Criteria in Solid Tumors [RECIST] v1.1). Secondary endpoints are objective response rate per RECIST v1.1, duration of response, disease control, overall survival, and safety. Sample size calculation is based on a median PFS of 3 months, based on historical data for anti–PD-1 monotherapy in the first-line treatment setting for PD-(L)1+ advanced/metastatic SCCHN. PFS, overall survival, and duration of response data will be analyzed by the Kaplan-Meier method. Patient enrollment is ongoing. Clinical trial information: NCT05287113.
Clinical status
Clinical
14 organizations
3 drugs
3 targets
Organization
Moores Cancer Center, UC San Diego HealthOrganization
University of California San DiegoOrganization
La Jolla, CAOrganization
Institut Curie, Saint Cloud, FranceOrganization
Paris, FranceOrganization
IncyteOrganization
Wilmington, DEOrganization
Incyte Biosciences International SarlOrganization
Morges, SwitzerlandOrganization
Head and Neck Cancer Medical Oncology 3 Unit, Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, ItalyOrganization
University of Milano, European Institute of Oncology, Division of Early Drug DevelopmentOrganization
Milan, ItalyDrug
INCAGN02385Drug
INCAGN02390Target
PD-1Target
LAG-3Target
TIM-3