A Study of INCMGA00012 in Metastatic Merkel Cell Carcinoma (POD1UM-201)

Study Overview
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Brief Summary
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The purpose of this study is to assess the clinical activity and safety of INCMGA00012 in participants with advanced/metastatic Merkel cell carcinoma (MCC).

Official Title
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A Phase 2 Study of INCMGA00012 in Participants With Metastatic Merkel Cell Carcinoma (POD1UM-201)

Conditions
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Metastatic Merkel Cell Carcinoma

Intervention / Treatment
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* Drug: Retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent. Diagnosis of MCC with distant metastatic disease or recurrent, advanced locoregional disease not amenable to surgery or radiation Eastern Cooperative Oncology Group performance status of 0 to 1. Measurable disease according to RECIST v1.1. Availability of tumor tissue (fresh or archival) for central pathology review. Willingness to avoid pregnancy or fathering children based on protocol-defined criteria. Exclusion Criteria: Prior systemic therapy for MCC, including chemotherapy and prior PD-1 or PD-L1-directed therapy. Treatment with anticancer drugs or participation in another interventional clinical study within 21 days before the first administration of study drug. Has not recovered to ≤ Grade 1 or baseline from toxic effects of prior therapy (with the exceptions for anemia not requiring transfusion support and any grade of alopecia) and/or complications from prior surgical intervention within 7 days before starting study treatment. Radiation therapy administered within 2 weeks of first dose of study treatment or radiation therapy to the thoracic region that is > 30 Gy within 6 months of the first dose of study treatment. Known central nervous system (CNS) metastases and/or carcinomatous meningitis. History of second malignancy within 3 years (with exceptions). Laboratory values outside the protocol-defined range at screening. Clinically significant pulmonary, cardiac, gastrointestinal or autoimmune disorders. Active bacterial, fungal, or viral infections, including hepatitis A, B, and C. Receipt of a live vaccine within 28 days of planned start of study therapy. Current use of protocol-defined prohibited medication. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). Inability or unlikely, in the opinion of the investigator, to comply with the Protocol requirements. Participant who is pregnant or breastfeeding.

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Retifanlimab: Chemotherapy: Naïve<br> | Drug: Retifanlimab<br>* INCMGA00012 administered at 500 milligrams (mg) by intravenous infusion once every 4 weeks<br>* Other names: INCMGA00012;|
| Experimental: Retifanlimab: Chemotherapy: Refractory<br> | Drug: Retifanlimab<br>* INCMGA00012 administered at 500 milligrams (mg) by intravenous infusion once every 4 weeks<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 confirmed overall response of complete response (CR) or partial response (PR), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1), as determined by Independent Central Radiographic Review (ICR), 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 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. | up to 26.8 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 PD, or death due to any cause, as determined by ICR. 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. A Kaplan-Meier estimate (estimated median) of the distribution function is reported. | up to 24.9 months | 
| Disease Control Rate (DCR) | DCR was defined as the percentage of participants with a confirmed overall response (CR and PR) or stable disease (SD) (non-CR/non-PD) lasting at least 6 months from the start of treatment, until the first PD or new anti-cancer therapy, per RECIST v1.1 as determined by ICR. 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. | up to 26.8 months | 
| Progression-free Survival (PFS) | According to RESIST v1.1, PFS was defined the time from the start of therapy until disease progression, or death due to any cause, as determined by ICR. Evaluation of target lesions: PD: ≥20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. The sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered PD). Evaluation of non-target lesions: PD: Unequivocal progression of existing non-target lesions. (Note: the appearance of one or more new lesions is also considered PD). | up to 26.8 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 33.9 months | 
| Number of Participants With Any Treatment-emergent Adverse Event (TEAE) | An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of study treatment. A TEAE was defined as either an AE reported for the first time or a worsening of a pre-existing event after the first dose of study drug until 90 days after the last dose of study drug. An AE with onset on/after starting a new anticancer therapy was not summarized as a TEAE. | up to 823 days (up to approximately 2.3 years) | 
| First-dose Cmax of Retifanlimab | Cmax was defined as the maximum observed plasma concentration. | preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| First-dose Cmin of Retifanlimab | Cmin was defined as the minimum observed plasma concentration over the dose interval. | preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| First-dose AUC0-t of Retifanlimab | AUC0-t was defined as the area under the plasma concentration-time curve from time zero to time t. | preinfusion, 10 minutes postinfusion (± 10 minutes), and 4 hours postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Metastatic merkel cell carcinoma, anti-PD-1 antibody, immunoglobulin G4 (IgG4) monoclonal antibody, INCMGA00012