A Study of INCMGA00012, INCB001158, and the Combination in Japanese Participants With Advanced Solid Tumors
- Conditions
- Advanced Solid TumorsMetastatic Solid Tumors
- Interventions
- Registration Number
- NCT03910530
- Lead Sponsor
- Incyte Biosciences Japan GK
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 18
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description INCB001158 100 mg INCB001158 Single-agent INCB001158. INCMGA00012 + INCB001158 Retifanlimab + INCB001158 Combination of INCMGA00012 and INCB001158. INCB001158 75 mg INCB001158 Single-agent INCB001158. INCMGA00012 Retifanlimab Single-agent INCMGA00012.
- Primary Outcome Measures
Name Time Method Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCMGA00012 Up to approximately 2 years Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Part 2: Number of treatment-emergent adverse events in participants receiving INCB001158 in combination with INCMGA00012 Up to approximately 2 years Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCB001158 Up to approximately 2 years Defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study drug.
- Secondary Outcome Measures
Name Time Method Part 1: Cmin of single-agent INCB001158 Up to 15 days Minimum observed plasma or serum concentration over the dose interval.
Part 1: t½ of single-agent INCMGA000012 Up to 15 days Apparent terminal-phase disposition half-life.
Part 1: Cmax of single-agent INCMGA000012 Up to 15 days Maximum observed plasma or serum concentration.
Part 1: Cmax of single-agent INCB001158 Up to 15 days Maximum observed plasma or serum concentration.
Part 1: Tmax of single-agent INCB001158 Up to 15 days Time to maximum concentration.
Part 1: Cmin of single-agent INCMGA000012 Up to 15 days Minimum observed plasma or serum concentration over the dose interval.
Part 1: AUCt of single-agent INCB001158 Up to 15 days Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Part 1: Tmax of single-agent INCMGA000012 Up to 15 days Time to maximum concentration.
Part 1: AUCt of single-agent INCMGA000012 Up to 15 days Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment Up to 15 days Maximum observed plasma or serum concentration.
Part 2: AUCt of INCMGA00012 and INCB001158 as a combination treatment Up to 15 days Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment Up to 15 days Time to maximum concentration.
Part 2: t½ of INCMGA00012 and INCB001158 as a combination treatment Up to 15 days Apparent terminal-phase disposition half-life.
Part 1 and Part 2: Overall response rate with INCMGA00012 in combination with INCB001158 Up to 2 years Defined as the percentage of participants experiencing a PR or CR as determined by the investigator according to RECIST v1.1.
Part 1 and Part 2: Disease control rate with single-agent INCMGA00012 Up to 2 years Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
Part 2: Cmin of INCMGA00012 and INCB001158 as a combination treatment Up to 15 days Minimum observed plasma or serum concentration over the dose interval.
Part 1 and Part 2: Overall response rate with single-agent INCMGA00012 Up to 2 years 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.
Part 1 and Part 2: Disease control rate with INCMGA00012 in combination with INCB001158 Up to 2 years Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
Part 1 and Part 2: Duration of response with single-agent INCMGA00012 Up to 2 years Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause.
Part 1 and Part 2: Duration of response with INCMGA00012 in combination with INCB001158 Up to 2 years Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause.
Part 1 and Part 2: Overall response rate with single-agent INCB001158 Up to 2 years Defined as the percentage of participants experiencing a PR or CR as determined by the investigator according to RECIST v1.1.
Part 1 and Part 2: Duration of response with single-agent INCB001158 Up to 2 years Defined as the time from first observed response until onset of disease progression according to RECIST v1.1 or death due to any cause.
Part 1: t½ of single-agent INCB001158 Up to 15 days Apparent terminal-phase disposition half-life.
Part 1 and Part 2: Disease control rate with single-agent INCB001158 Up to 2 years Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
Trial Locations
- Locations (2)
National Cancer Center Hospital East
🇯🇵Kashiwa, Japan
National Cancer Center Hospital
🇯🇵Chuo Ku, Japan