INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Study Overview
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Brief Summary
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The purpose of this study is to determine the safety, tolerability, efficacy, PK and pharmacodynamics of INCAGN01876 when given in combination with retifanlimab. The study will consist of 2 parts: a safety lead-in part (Part 1) followed by a dose expansion part (Part 2).

Detailed Description
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The purpose of this study is to determine the safety, tolerability, efficacy, PK and pharmacodynamics of INCAGN01876 when given in combination with retifanlimab in participants with GITR expression in recurrent or metastatic HNSCC who have progressed on or after prior systemic therapy including anti-PD-(L)1 therapy. The study will consist of 2 parts: a safety lead-in part (Part 1) followed by a dose expansion part (Part 2)

Official Title
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Phase 2, Open-Label, Multicenter Study of INCAGN01876 in Combination With Immunotherapy in Participants With Recurrent or Metastatic Head and Neck Squamous Cell Carcinoma

Conditions
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Metastatic Head and Neck Squamous Cell Carcinoma, Advanced Malignancies, Recurrent Head and Neck Squamous Cell Carcinoma

Intervention / Treatment
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* Biological: INCAGN01876
* Biological: retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Histologically or cytologically confirmed recurrent or metastatic HNSCC (oral cavity, oropharynx, hypopharynx, or larynx), that is not amenable to local therapy with curative intent (surgery or radiation therapy with or without chemotherapy). Participants with squamous cell carcinomas of the nasopharynx, salivary gland, or nonsquamous cell histology are excluded. Documented progression on or after PD-(L)1 inhibitor alone or in combination with platinum-based chemotherapy for recurrent or metastatic HNSCC. Exception: Treatment Group B (Part 2, expansion): PD-(L)1-naïve. ECOG performance status of 0 to 1. Measurable disease based on RECIST v1.1. Mandatory pre-treatment and on-treatment tumor biopsies. GITR-positive tumor confirmed by central laboratory before study treatment start. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Have received chemotherapy, targeted small molecule therapy or curative radiation within 21 days of first dose of study drug; prior mAB for anticancer therapy other within 28 days of first dose of study drug; or investigational study drugs or devices within 28 days or five half-lives prior to enrollment unless approved by medical monitor. Prior treatment with any TNF Super Family agonist therapy. Have not recovered to ≤ Grade 1 from toxic effects of prior therapy. Laboratory and medical history parameters not within the Protocol-defined range before the first administration of study treatment. Known active HBV or HCV, or Known to be seropositive for HIV. Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Have an active autoimmune disease that has required systemic treatment in past 2 years (i.e., with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Known active infections requiring systemic treatment.

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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: Cohort 1<br>INCAGN01876 every 2 weeks (Q2W) with retifanlimab every 4 weeks (Q4W). | Biological: INCAGN01876<br>* INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.<br>Biological: retifanlimab<br>* retifanlimab will be administered via IV Q4W<br>|
| Experimental: Part 1: Cohort 2<br>INCAGN01876 Q2W with retifanlimab Q4W. | Biological: INCAGN01876<br>* INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.<br>Biological: retifanlimab<br>* retifanlimab will be administered via IV Q4W<br>|
| Experimental: Part 2 (Expansion): Treatment Group A<br>INCAGN01876 and retifanlimab combination in participants who have been previously treated with anti-PD-(L)1 therapy. | Biological: INCAGN01876<br>* INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.<br>Biological: retifanlimab<br>* retifanlimab will be administered via IV Q4W<br>|
| Experimental: Part 2 (Expansion): Treatment Group B<br>INCAGN01876 and retifanlimab combination in participants who are naive to anti-PD-(L)1 therapy. | Biological: INCAGN01876<br>* INCAGN1876 will be adminstered via IV at at the protocol-defined dose and schedule according to cohort and treatment group enrollment.<br>Biological: retifanlimab<br>* retifanlimab will be administered via IV Q4W<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Participants With Treatment-Emergent Adverse Events (TEAEs) | A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment. | Screening through 90 days after end of treatment, up to 24 months | 
| Objective response rate (ORR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 | Defined as the percentage of participants having complete response (CR) or partial response (PR). | Assessed every 8 weeks for 12 months, thereafter every 12 weeks up to the end of treatment, up to 24 months. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of response (DOR) based on RECIST v1.1 and mRECIST | Defined as the time from the earliest date of disease response (CR or PR) until earliest date of disease progression or death due to any cause. | Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. | 
| Disease control rate (DCR) based on RECIST v1.1 and mRECIST | Defined as the percentage of participants having CR, PR, or stable disease (SD). | Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. | 
| Progression-free survival (PFS) based on RECIST v1.1 and mRECIST | Defined as the time from the start of combination therapy until the earliest date of disease progression or death due to any cause. | Assessed every 8 weeks for 12 months, then every 12 weeks, up to 24 months. | 
| Part 2: Participants With Treatment-Emergent Adverse Events (TEAEs) | A TEAE is any adverse event (AE) either reported for the first time or worsening of a pre-existing event after the first dose of study treatment. | Screening through 90 days after end of treatment, up to 24 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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carcinoma, carcinoma, squamous cell, squamous cell carcinoma of head and neck, anti-PD-(L)1 therapy, HNSCC, SCCHN