A Study of INCMGA00012 in Squamous Carcinoma of the Anal Canal Following Platinum-Based Chemotherapy (POD1UM-202)

Study Overview
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Brief Summary
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The purpose of this study is to assess the efficacy of INCMGA00012 in participants with locally advanced or metastatic squamous carcinoma of the anal canal (SCAC) who have progressed after platinum-based chemotherapy.

Official Title
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A Phase 2 Study of INCMGA00012 in Participants With Squamous Carcinoma of the Anal Canal Who Have Progressed Following Platinum-Based Chemotherapy (POD1UM-202)

Conditions
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Squamous Cell Carcinoma of Anal Canal

Intervention / Treatment
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* Drug: Retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Ability to comprehend and willingness to sign a written informed consent form. Confirmed diagnosis of locally advanced or metastatic SCAC. Must have received (or been intolerant to or ineligible for) at least 1 prior line of platinum-based chemotherapy and received no more than 2 prior systemic treatments. Must have measurable disease by RECIST v1.1. Eastern Cooperative Oncology Group performance status of 0 to 1. If HIV-positive, then all of the following criteria must also be met: CD4+ count ≥ 300/μL, undetectable viral load, and receiving highly active antiretroviral therapy. Exclusion Criteria: Receipt of anticancer therapy or participation in another interventional clinical study within 21 days before the first administration of study drug; 6 weeks for mitomycin C. Radiotherapy within 14 days of first dose of study treatment with the following caveats: 28 days for pelvic radiotherapy, 6 months for thoracic region radiotherapy that is > 30 Gy. Prior treatment with programmed cell death protein 1 (PD-1) or programmed cell death ligand protein 1 (PD-L1)-directed therapy. Active autoimmune disease requiring systemic immunosuppression. Known central nervous system (CNS) metastases and/or carcinomatous meningitis. Known active hepatitis infection. Active infections requiring systemic therapy. Is pregnant or breastfeeding or is expecting to conceive or father children within the projected duration of the study, from screening through 6 months after the last dose of study drug.

Ages Eligible for Study
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Minimum Age: 18 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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retifanlimab 500 mg<br>Retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W). | Drug: Retifanlimab<br>* Retifanlimab 500 milligrams (mg) intravenously every 4 weeks (Q4W).<br>* Other names: INCMGA00012;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as assessed by independent central radiographic (ICR) review, at any post-Baseline visit until new anti-cancer therapy or first Progressive Disease. 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. | Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR was defined as the time from an initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by ICR, or death due to any cause. 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 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. PD: progression of a target or non-target lesion or presence of a new lesion. | up to 18.2 months | 
| Disease Control Rate (DCR) | DCR was defined as the percentage of participants with a confirmed overall response of CR, PR, or stable disease (SD), per RECIST v1.1, at any post-baseline visit until the first progressive disease (PD) or new anti-cancer 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 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. PD: progression of a target or non-target lesion or presence of a new lesion. SD: no change in target lesions to qualify for CR, PR, or PD. | Cycle 1 Day 1, and every 4 weeks throughout the study, up to approximately 24 months | 
| Progression-free Survival (PFS) | According to RECIST 1.1, PFS was defined as the length of time from the initial infusion of study drug until the earliest date of disease progression, as determined by ICR, or death due to any cause, if occurring sooner than progression. | up to 16.8 months | 
| Overall Survival | Overall survival was defined as the time in months between the first dose date (Day 1) and the date of death due to any cause. | up to 28.2 months | 
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug-related. An AE could have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of the study drug. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of retifanlimab and within 90 days of the last administration of retifanlimab. | up to 913 days | 
| Cmax of Retifanlimab | Cmax was defined as the maximum observed plasma concentration. | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | 
| Tmax of Retifanlimab | tmax was defined as the time to the maximum concentration. | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | 
| Cmin of Retifanlimab | Cmin was defined as the minimum observed plasma concentration over the dose interval. | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | 
| AUC0-t of Retifanlimab | AUC0-t was defined as the area under the plasma concentration-time curve from time = 0 to the last measurable concentration at time = t. | pre-infusion on Day 1 of Cycles 1, 2, 4, 6, and 7; 10 minutes and 4 hours post-infusion on Day 1 of Cycles 1 and 6 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous carcinoma of the anal canal, anti-PD-1 antibody, IgG4 monoclonal antibody, INCMGA00012