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

Study Overview
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Brief Summary
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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).

Official Title
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A Randomized, Double-Blind, Multicenter, Phase 2 Study of Retifanlimab in Combination With INCAGN02385 (Anti-LAG-3) and INCAGN02390 (Anti-TIM-3) as First-Line Treatment in Participants With PD-L1-Positive (CPS ≥ 1) Recurrent/Metastatic Squamous Cell Carcinoma of the Head and Neck

Conditions
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Head and Neck Cancer

Intervention / Treatment
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* Drug: Retifanlimab
* Drug: INCAGN02385
* Drug: INCAGN02390
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 99 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Patients will be randomized to 1 of 3 treatment groups.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Treatment Group 1: Retifanlimab Monotherapy<br>Retifanlimab will be administered intravenously every 4 weeks. Placebos for INCAGN02385 and INCAGN02390 will be administered intravenously every 2 weeks. | Drug: Retifanlimab<br>* Retifanlimab 500mg will be administered intravenously every 4 weeks.<br>Drug: Placebo<br>* Placebo will be administered intravenously.<br>|
| Experimental: Treatment Group 2: Retifanlimab + INCAGN02385<br>Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and Placebo for INCAGN02390 will be administered intravenously every 2 weeks. | Drug: Retifanlimab<br>* Retifanlimab 500mg will be administered intravenously every 4 weeks.<br>Drug: INCAGN02385<br>* INCAGN02385 350mg will be administered intravenously every 2 weeks.<br>Drug: Placebo<br>* Placebo will be administered intravenously.<br>|
| Experimental: Treatment Group 3: Retifanlimab + INCAGN02385 + INCAGN02390<br>Retifanlimab plus INCAGN02385 and INCAGN02390 will be administered intravenously. Retifanlimab will be administered intravenously every 4 weeks. INCAGN02385 and INCAGN02390 will be administered every 2 weeks. | Drug: Retifanlimab<br>* Retifanlimab 500mg will be administered intravenously every 4 weeks.<br>Drug: INCAGN02385<br>* INCAGN02385 350mg will be administered intravenously every 2 weeks.<br>Drug: INCAGN02390<br>* INCAGN02390 400 mg will be administered intravenously every 2 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Progression Free Survival (PFS) | Defined as the interval between the date of first dose of study treatment and the earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death due to any cause. | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | Defined as having a Complete Response (CR) or Partial Response (PR), determined based on investigator assessment per RECIST v1.1. | Up to 24 months | 
| Duration of Response (DOR) | Defined as the time from earliest date of disease response (CR or PR) until earliest date of disease progression, based on investigator assessment per RECIST v1.1, or death from any cause if occurring sooner than progression. | Up to 24 months | 
| Disease Control Rate (DCR) | Defined as having CR, PR, or SD (≥ 6 months) as best response, based on investigator assessment per RECIST v1.1. | Up to 24 months | 
| Overall Survival (OS) | Defined as the interval between the date of the date of first dose of study treatment until death due to any cause. | Up to 36 months | 
| Participants with treatment-emergent adverse events (TEAE) | TEAE is defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug | Up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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squamous cell carcinoma of the head and neck (SCCHN), INCAGN02385, INCAGN02390, Retifanlimab, IgG1κ monoclonal antibody, LAG-3, TIM-3, PD-1, PD-L1