A Study of INCMGA00012 in Participants With Selected Solid Tumors (POD1UM-203)

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 solid tumors where the efficacy of PD-1 inhibitors has previously been established.

Official Title
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A Phase 2 Study of INCMGA00012 (PD-1 Inhibitor) in Participants With Selected Solid Tumors (POD1UM-203)

Conditions
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Metastatic Non-small Cell Lung Cancer, Locally Advanced Urothelial Cancer, Metastatic Urothelial Cancer, Unresectable Melanoma, Metastatic Melanoma, Locally Advanced Renal Cell Carcinoma, Metastatic Clear-Cell Renal Cell Carcinoma

Intervention / Treatment
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* Drug: Retifanlimab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Confirmed diagnosis of one of the following: treatment-naïve metastatic non-small cell lung cancer with high PD-L1 expression (tumor proportion score ≥ 50%) and no epidermal growth factor receptor (EGFR), alkaline phosphatase (ALK), or ROS activating genomic tumor aberrations; locally advanced or metastatic urothelial carcinoma in participants who are not eligible for cisplatin therapy and whose tumors express PD-L1 with a combined positive score ≥ 10; unresectable or metastatic melanoma; locally advanced or metastatic renal cell carcinoma with clear cell component (with or without sarcomatoid features) and having received no prior systemic therapy. Measurable disease per RECIST v1.1. Eastern Cooperative Oncology Group performance status 0 to 1. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Receipt of anticancer therapy or participation in another interventional clinical study within 21 days before the first administration of study drug. Prior treatment with PD-1 or PD-L1 directed therapy (other immunotherapies may be acceptable with prior approval from the medical monitor). 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. Toxicity of prior therapy that has not recovered to ≤ Grade 1 or baseline (with the exception of anemia not requiring transfusion support and any grade of alopecia). Endocrinopathy, if well-managed, is not exclusionary and should be discussed with sponsor medical monitor. Has not recovered adequately from toxicities and/or complications from surgical intervention before starting study drug. Laboratory values outside the protocol-defined range at screening. Known additional malignancy that is progressing or requires active treatment, or history of other malignancy within 3 years of study entry. Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). Evidence of interstitial lung disease or active noninfectious pneumonitis. Known active central nervous system metastases and/or carcinomatous meningitis. Known active hepatitis B antigen, hepatitis B virus, or hepatitis C virus infection. Active infections requiring systemic therapy. Known to be HIV-positive, unless all of the following criteria are met: CD4+ count ≥ 300/μL, undetectable viral load, receiving antiretroviral therapy. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures (eg, antihistamines and corticosteroids). Impaired cardiac function or clinically significant cardiac disease. Is pregnant or breastfeeding. Has received a live vaccine within 28 days of the planned start 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
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Melanoma: retifanlimab 500 mg<br>Participants with melanoma received retifanlimab 500 milligrams (mg) every 4 weeks (Q4W), administered by intravenous (IV) infusion over 30 minutes on Day 1 of each 28-day cycle. | Drug: Retifanlimab<br>* Retifanlimab administered intravenously at 500 mg every 4 weeks<br>* Other names: INCMGA00012;|
| Experimental: NSCLC: retifanlimab 500 mg<br>Participants with non-small cell lung cancer (NSCLC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. | Drug: Retifanlimab<br>* Retifanlimab administered intravenously at 500 mg every 4 weeks<br>* Other names: INCMGA00012;|
| Experimental: UC: retifanlimab 500 mg<br>Participants with urethelial carcinoma (UC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. | Drug: Retifanlimab<br>* Retifanlimab administered intravenously at 500 mg every 4 weeks<br>* Other names: INCMGA00012;|
| Experimental: RCC: retifanlimab 500 mg<br>Participants with renal cell carcinoma (RCC) received retifanlimab 500 mg Q4W, administered by IV infusion over 30 minutes on Day 1 of each 28-day cycle. | Drug: Retifanlimab<br>* Retifanlimab administered intravenously at 500 mg 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 |
| --- | --- | --- |
| Overall 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 determined by the investigator, 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. | up to 25.9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of Response (DOR) | DOR was defined as the time from initial objective response (CR or PR) per RECIST v1.1 until the first observation of documented disease progression (PD), as determined by the investigator, 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 24.0 months | 
| Disease Control Rate (DCR) | DCR was defined as the proportion of participants with an overall response of CR, PR, or stable disease (SD), per RECIST v1.1. 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 25.9 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, determined by investigator assessment, or death due to any cause, if occurring sooner than progression. | up to 25.9 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 therefore have been any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of 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 until the earlier of 90 days of the last administration of retifanlimab and new anti-cancer therapy start if any, are reported. | up to approximately 2.3 years | 
| First-dose Cmax of Retifanlimab | Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| Cmax of Retifanlimab at Steady-state | Cmax was defined as the maximum observed plasma or serum concentration of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days) | 
| First-dose Tmax of Retifanlimab | tmax was defined as the time to the maximum concentration of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| Tmax of Retifanlimab at Steady-state | tmax was defined as the time to the maximum concentration of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days) | 
| First-dose Cmin of Retifanlimab | Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| Cmin of Retifanlimabv at Steady-state | Cmin was defined as the minimum observed plasma or serum concentration over the dose interval of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days) | 
| First-dose AUC0-t of Retifanlimab | AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycle 1 | 
| AUC0-t of Retifanlimab at Steady-state | AUC0-t was defined as the area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t of retifanlimab. | preinfusion and 10 minutes postinfusion (± 10 minutes) on Day 1 of Cycles 1, 2, 4, and 6 (up to approximately 168 days; each cycle was 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PD-1inhibitor, non-small cell lung cancer, urothelial cancer, melanoma, renal cell carcinoma