Advanced Solid Tumors, Metastatic Solid Tumors
Conditions
Keywords
Advanced solid tumors, metastatic solid tumors, INCMGA00012, INCB001158, Japan, PD-1 Inhibitor, Arginase Inhibitor
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.
Interventions
DRUGINCB001158
Part 1: INCB001158 75 or 100 mg twice daily administered orally.
DRUGRetifanlimab
Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.
DRUGRetifanlimab + INCB001158
Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 .
Sponsors
Incyte Biosciences Japan GK
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 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. |
| 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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 INCMGA000012 | Up to 15 days | Time to maximum 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: Cmin of single-agent INCB001158 | Up to 15 days | Minimum observed plasma or serum concentration over the dose interval. |
| 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 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: t½ of single-agent INCMGA000012 | Up to 15 days | Apparent terminal-phase disposition half-life. |
| Part 1: t½ of single-agent INCB001158 | Up to 15 days | Apparent terminal-phase disposition half-life. |
| Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment | Up to 15 days | Maximum observed plasma or serum concentration. |
| Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment | Up to 15 days | Time to maximum concentration. |
| 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 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: 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 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: 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: 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 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. |
| 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 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 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. |
Countries
Japan
Outcome results
None listed