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

Incyte Biosciences Japan GK18 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumors Metastatic Solid Tumors

Interventions

RetifanlimabDRUG

Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.

INCB001158DRUG

Part 1: INCB001158 75 or 100 mg twice daily administered orally.

Retifanlimab + INCB001158DRUG

Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 .

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (2)

National Cancer Center Hospital

Chūōku, Japan

National Cancer Center Hospital East

Kashiwa, Japan

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Up to approximately 2 years

Secondary Outcomes

Part 1: Cmax of single-agent INCMGA000012

Maximum observed plasma or serum concentration.

Time frame: Up to 15 days

Part 1: Cmax of single-agent INCB001158

Maximum observed plasma or serum concentration.

Time frame: Up to 15 days

Part 1: Tmax of single-agent INCMGA000012

Time to maximum concentration.

Time frame: Up to 15 days

Part 1: Tmax of single-agent INCB001158

Time to maximum concentration.

Time frame: Up to 15 days

Data from ClinicalTrials.gov

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Part 1: Cmin of single-agent INCMGA000012

Minimum observed plasma or serum concentration over the dose interval.

Time frame: Up to 15 days

Part 1: Cmin of single-agent INCB001158

Minimum observed plasma or serum concentration over the dose interval.

Time frame: 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.

Time frame: 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.

Time frame: Up to 15 days

Part 1: t½ of single-agent INCMGA000012

Apparent terminal-phase disposition half-life.

Time frame: Up to 15 days

Part 1: t½ of single-agent INCB001158

Apparent terminal-phase disposition half-life.

Time frame: Up to 15 days

Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment

Maximum observed plasma or serum concentration.

Time frame: Up to 15 days

Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment

Time to maximum concentration.

Time frame: 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.

Time frame: 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.

Time frame: Up to 15 days

Part 2: t½ of INCMGA00012 and INCB001158 as a combination treatment

Apparent terminal-phase disposition half-life.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: 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.

Time frame: Up to 2 years