Study of Retinfanlimab in Combination With INCAGN02385 and INCAGN02390 as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Phase 2Active Not RecruitingNCT05287113

Incyte Biosciences International Sàrl176 enrolled

Overview

The purpose of this study is to evaluate the safety and efficacy of the combination of retifanlimab plus INCAGN02385 and retifanlimab plus INCAGN02385 and INCAGN02390 compared with retifanlimab alone as first-line treatment in PD-L1-positive and systemic therapy-naive recurrent/metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

176

Conditions

Head and Neck Cancer

Interventions

RetifanlimabDRUG

Retifanlimab 500mg will be administered intravenously every 4 weeks.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Histologically or cytologically confirmed R/M SCCHN that is not amenable to therapy with curative intent. Participants who refuse potentially curative salvage surgery for recurrent disease are ineligible. * Eligible primary tumor locations are oropharynx, oral cavity, hypopharynx, and larynx. * Participants must not have received prior systemic therapy for R/M SCCHN. * PD-L1 positive tumor status defined by CPS ≥ 1% per central laboratory determination. * For participants with primary oropharyngeal tumors, documentation of HPV p16 status based on local institutional standard is required. HPV p16 status is not required for other eligible SCCHN primary tumor sites. * Participant must have at least 1 measurable tumor lesion per RECIST v1.1. * Availability of archival tissue for biomarker analysis from a core or excisional biopsy or willingness to undergo a fresh biopsy. * ECOG performance status of 0 or 1. * Willingness to avoid pregnancy or fathering children. Exclusion Criteria: * Progressive or recurrent disease within 6 months of the last dose of systemic treatment for locally advanced SCCHN. Prior PD-(L)1, LAG-3, or TIM-3 directed therapy, or any other checkpoint inhibitor therapy, for SCCHN or any other malignancy. * Treatment with anticancer therapies or participation in another interventional clinical study within 21 days before the first administration of study treatment. * Presence of tumors that invade major blood vessels, as shown unequivocally by imaging, and with active bleeding. * Participants with primary tumors of the nasopharynx, sinonasal cavity, or salivary and are excluded. * Less than 3-month life expectancy. * Participant has not recovered to ≤ Grade 1 or baseline from residual toxicities of prior therapy. * Participant has not recovered adequately from toxicities and/or complications from surgical intervention before starting study treatment. * Palliative radiation therapy administered within 1 week before the first dose of study treatment or radiation therapy in the thoracic region that is \> 30 Gy within 6 months before the first dose of study treatment. * Known active CNS metastases and/or carcinomatous meningitis. Participants will be excluded if it has been \< 4 weeks since radiation therapy was delivered to the CNS.

Locations (91)

Mayo Clinic Rochester

Scottsdale, Arizona, United States

City of Hope National Medical Center

Duarte, California, United States

City of Hope Orange County

Irvine, California, United States

University of California San Diego Medical Center, Moores Cancer Center

La Jolla, California, United States

City of Hope-Antelope Valley

Lancaster, California, United States

Outcomes

Primary Outcomes

Progeression-free Survival (PFS)

PFS was defined as the time from the date of randomization to the date of the first documented progression, as determined by investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), or death due to any cause, whichever occurred first.

Time frame: up to 738 days

Secondary Outcomes

Objective Response

Objective response was defined as having a complete response (CR) or partial response (PR), determined based on investigator assessment per RECIST v1.1, recorded post-baseline before and including the first progressive disease, and before new anticancer therapy. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.