A Study of INCMGA00012, INCB001158, and the Combination in Japanese Participants With Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and tolerability and the pharmacokinetics (PK) of INCMGA00012 (PD-1 Inhibitor), INCB001158 (Arginase Inhibitor), and the combination in Japanese participants with advanced solid tumor malignancies.

Official Title
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A Phase 1b Study of INCMGA00012 (PD-1 Inhibitor), INCB001158 (Arginase Inhibitor), and the Combination in Japanese Participants With Advanced Solid Tumors

Conditions
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Advanced Solid Tumors, Metastatic Solid Tumors

Intervention / Treatment
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* Drug: Retifanlimab
* Drug: INCB001158
* Drug: Retifanlimab + INCB001158


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant is Japanese Histologically or cytologically confirmed diagnosis of any locally advanced or metastatic solid tumors not amenable to local or other curative therapy. Participants with nonevaluable lesions are allowed. Life expectancy > 3 months. Eastern Cooperative Oncology Group performance status 0 to 1. Female participants agree to use medically acceptable contraceptive measures, should not be breastfeeding, and must have a negative pregnancy test before the start of study drug administration. Female participants of childbearing potential must understand and accept that pregnancy must be avoided during participation in the study. Male participants should avoid unprotected sex with women of childbearing potential and refrain from donating sperm during participation the study. Exclusion Criteria: Receipt of anticancer therapy or participation in another interventional clinical study within 14 days before the first administration of study drug with the following exceptions: Immunotherapy or biological therapy (eg, monoclonal antibodies) within 21 days the first administration of study drug; 6 weeks for mitomycin-C or nitrosoureas; 7 days for tyrosine kinase inhibitors. Radiotherapy within 14 days of first dose of study treatment with the following exceptions: 28 days for pelvic radiotherapy; 6 months for thoracic region radiotherapy that is > 30 Gy. Toxicity of prior therapy and/or complications from surgical intervention that has not recovered to ≤ Grade 1 or baseline within 7 days before starting study drug treatment (with the exception of anemia not requiring transfusion support and any grade of alopecia). Note: Endocrinopathy, if well-managed, is not exclusionary and should be discussed with sponsor medical monitor. Receipt of prior systemic treatment with an arginase inhibitor Immune-related toxicity during prior checkpoint inhibitor therapy for which permanent discontinuation of therapy is recommended (per product label or consensus guidelines), OR any immune-related toxicity requiring intensive or prolonged immunosuppression to manage (with the exception of endocrinopathy that is well controlled on replacement hormones). Active autoimmune disease requiring systemic immunosuppression in excess of physiologic maintenance doses of corticosteroids (> 10 mg of prednisone or equivalent). Known active central nervous system metastases and/or carcinomatous meningitis. Known active hepatitis A virus, hepatitis B virus, or hepatitis C virus infection. Known HIV infection. Active infections requiring systemic therapy. Known hypersensitivity to another monoclonal antibody that cannot be controlled with standard measures and/or known hypersensitivity ≥ Grade 3, or severe reaction, to study treatments or any of their excipients or additives. Participants with impaired cardiac function or clinically significant cardiac disease. Evidence of interstitial lung disease or active, noninfectious pneumonitis or a history of interstitial lung disease. Participant 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: INCMGA00012<br>Single-agent INCMGA00012. | Drug: Retifanlimab<br>* Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.<br>* Other names: INCMGA00012;|
| Experimental: INCB001158 75 mg<br>Single-agent INCB001158. | Drug: INCB001158<br>* Part 1: INCB001158 75 or 100 mg twice daily administered orally.<br>|
| Experimental: INCB001158 100 mg<br>Single-agent INCB001158. | Drug: INCB001158<br>* Part 1: INCB001158 75 or 100 mg twice daily administered orally.<br>|
| Experimental: INCMGA00012 + INCB001158<br>Combination of INCMGA00012 and INCB001158. | Drug: Retifanlimab + INCB001158<br>* Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 .<br>* Other names: INCMGA00012;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCMGA00012 | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to approximately 2 years | 
| Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCB001158 | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to approximately 2 years | 
| Part 2: Number of treatment-emergent adverse events in participants receiving INCB001158 in combination with INCMGA00012 | Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug. | Up to approximately 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Part 1: Cmax of single-agent INCMGA000012 | Maximum observed plasma or serum concentration. | Up to 15 days | 
| Part 1: Cmax of single-agent INCB001158 | Maximum observed plasma or serum concentration. | Up to 15 days | 
| Part 1: Tmax of single-agent INCMGA000012 | Time to maximum concentration. | Up to 15 days | 
| Part 1: Tmax of single-agent INCB001158 | Time to maximum concentration. | Up to 15 days | 
| Part 1: Cmin of single-agent INCMGA000012 | Minimum observed plasma or serum concentration over the dose interval. | Up to 15 days | 
| Part 1: Cmin of single-agent INCB001158 | Minimum observed plasma or serum concentration over the dose interval. | Up to 15 days | 
| Part 1: AUCt of single-agent INCMGA000012 | Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t. | Up to 15 days | 
| Part 1: AUCt of single-agent INCB001158 | Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t. | Up to 15 days | 
| Part 1: t½ of single-agent INCMGA000012 | Apparent terminal-phase disposition half-life. | Up to 15 days | 
| Part 1: t½ of single-agent INCB001158 | Apparent terminal-phase disposition half-life. | Up to 15 days | 
| Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment | Maximum observed plasma or serum concentration. | Up to 15 days | 
| Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment | Time to maximum concentration. | Up to 15 days | 
| Part 2: Cmin of INCMGA00012 and INCB001158 as a combination treatment | Minimum observed plasma or serum concentration over the dose interval. | Up to 15 days | 
| Part 2: AUCt of INCMGA00012 and INCB001158 as a combination treatment | Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t. | Up to 15 days | 
| Part 2: t½ of INCMGA00012 and INCB001158 as a combination treatment | Apparent terminal-phase disposition half-life. | Up to 15 days | 
| Part 1 and Part 2: Overall response rate with single-agent INCMGA00012 | Defined as the percentage of participants experiencing a partial response (PR) or complete response (CR) as determined by the investigator according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Up to 2 years | 
| Part 1 and Part 2: Overall response rate with single-agent INCB001158 | Defined as the percentage of participants experiencing a PR or CR as determined by the investigator according to RECIST v1.1. | Up to 2 years | 
| Part 1 and Part 2: Overall response rate with INCMGA00012 in combination with INCB001158 | Defined as the percentage of participants experiencing a PR or CR as determined by the investigator according to RECIST v1.1. | Up to 2 years | 
| Part 1 and Part 2: Disease control rate with single-agent INCMGA00012 | Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1. | Up to 2 years | 
| Part 1 and Part 2: Disease control rate with single-agent INCB001158 | Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1. | Up to 2 years | 
| Part 1 and Part 2: Disease control rate with INCMGA00012 in combination with INCB001158 | Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1. | Up to 2 years | 
| Part 1 and Part 2: Duration of response with single-agent INCMGA00012 | Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause. | Up to 2 years | 
| Part 1 and Part 2: Duration of response with single-agent INCB001158 | Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause. | Up to 2 years | 
| Part 1 and Part 2: Duration of response with INCMGA00012 in combination with INCB001158 | Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause. | Up to 2 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced solid tumors, metastatic solid tumors, INCMGA00012, INCB001158, Japan, PD-1 Inhibitor, Arginase Inhibitor