Carboplatin-paclitaxel With Retifanlimab or Placebo in Participants With Locally Advanced or Metastatic Squamous Cell Anal Carcinoma (POD1UM-303/InterAACT 2).

Study Overview
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Brief Summary
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This study is a Phase 3 global, multicenter, placebo-controlled double-blind randomized study that will enroll participants with inoperable locally recurrent or metastatic SCAC not previously treated with systemic chemotherapy.

Official Title
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A Phase 3 Global, Multicenter, Double-Blind Randomized Study of Carboplatin-Paclitaxel With INCMGA00012 or Placebo in Participants With Inoperable Locally Recurrent or Metastatic Squamous Cell Carcinoma of the Anal Canal Not Previously Treated With Systemic Chemotherapy (POD1UM-303/InterAACT 2)

Conditions
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Squamous Cell Carcinoma of the Anal Canal

Intervention / Treatment
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* Drug: carboplatin
* Drug: paclitaxel
* Drug: retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Able to comprehend and willing to sign a written ICF for the study. Are 18 years of age or older (or as applicable per local country requirements). Histologically or cytologically verified, inoperable locally recurrent or metastatic SCAC. No prior systemic therapy other than the following: a. Chemotherapy administered concomitantly with radiotherapy as a radiosensitizing agent is permitted. b. Prior neoadjuvant or adjuvant therapy if completed ≥ 6 months before study entry. Has measurable disease per RECIST v1.1 as determined by local site investigator/radiology assessment. Tumor lesions situated in a previously irradiated area, or in an area subjected to other loco-regional therapy, are usually not considered measurable unless there has been demonstrated progression in the lesion. Able and willing to provide adequate tissue sample and whole blood sample with central testing result prior to randomization. Biopsy for archival samples should have occurred within 9 months prior to randomization. ECOG performance status 0 to 1. If HIV-positive, then must be stable as defined by: a. CD4+ count ≥ 200/μL, b. Undetectable viral load per standard of care assay, c. Receiving antiretroviral therapy (ART/HAART) for at least 4 weeks prior to study enrollment, and have not experienced any HIV-related opportunistic infection for at least 4 weeks prior to study enrollment. Willingness to avoid pregnancy or fathering children Exclusion Criteria: Has received prior PD-(L)1 directed therapy Has received prior radiotherapy with or without radiosensitizing chemotherapy within 28 days of Cycle 1 Day 1 except for palliative radiation (30 Gy or less) which is restricted for 14 days of Cycle 1 Day 1 (note: all toxicities associated should have resolved to Grade ≤ 1). Participants with laboratory outside of the protocol defined ranges. History of second malignancy within 3 years (with exceptions). Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders. Active bacterial, fungal, or viral infections, including hepatitis A, B, and C and IV antibiotic use within 7 days of Cycle 1 Day 1. Receipt of a live vaccine within 28 days of planned start of study therapy. History of organ transplant, including allogeneic stem cell transplantation. Known active CNS metastases and/or carcinomatous meningitis. Known hypersensitivity to platinum, paclitaxel, another monoclonal antibody, or any of the excipients that cannot be controlled with standard measures (eg, antihistamines, corticosteroids). Participant is pregnant or breastfeeding. Current use of protocol defined prohibited medication. Has pre-existing peripheral neuropathy that is ≥ Grade 2 by CTCAE v5. Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Group A : carboplatin+paclitaxel+placebo<br>Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and placebo on Day 1 of each 28 day cycle | Drug: carboplatin<br>* carboplatin will be administered intravenous on Day 1 of each 28 day cycle<br>Drug: paclitaxel<br>* paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle<br>|
| Experimental: Group B : carboplatin+paclitaxel+retifanlimab<br>Participants will receive carboplatin on Day 1,paclitaxel on Day1,8, 15, and retifanlimab on Day 1 of each 28 day cycle | Drug: carboplatin<br>* carboplatin will be administered intravenous on Day 1 of each 28 day cycle<br>Drug: paclitaxel<br>* paclitaxel will be administered intravenous on Days 1,8, and 15 of each 28 day cycle<br>Drug: retifanlimab<br>* retifanlimab will be administered intravenous on Day 1 of each 28 day cycle<br>* Other names: INCMGA00012;|

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 time from the date of randomization until disease progression according to RECIST v1.1 by BICR or death due to any cause. | up to 4.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Survival (OS) | Defined as the time from the date of randomization until death due to any cause. | Up to 4.5 years | 
| Overall Response Rate (ORR) | Defined as the proportion of participants who have a confirmed complete response or partial response per RECIST v1.1 based on BICR. | Up to 4.5 years | 
| Duration of Response (DOR) | Defined as the time from the earliest date of documented response until earliest date of disease progression (per RECIST v1.1 based on BICR) or death from any cause, whichever comes first. | Up to 4.5 years | 
| Disease Control Rate(DCR) | Defined as the number of participants maintaining either an ORR or stable disease. | Up to 4.5 years | 
| Number of treatment-emergent adverse events | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment up to 90 days after last dose of study treatment. | Up to 4.5 years | 
| Cmax of retifanlimab when administered with chemotherapy | Maximum observed plasma or serum concentration. | Up to 4.5 years | 
| tmax of retifanlimab when administered with chemotherapy | Time to maximum concentration | Up to 4.5 years | 
| Cmin of retifanlimab when administered with chemotherapy | Minimum observed plasma or serum concentration over the dose interval | Up to 4.5 years | 
| AUC0-t of retifanlimab when administered with chemotherapy | Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t | Up to 4.5 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Squamous cell carcinoma, carboplatin, paclitaxel, PD-1 Inhibitor, Anal Cancer, SCAC