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

Advanced Solid Tumors Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03910530
• Other study ID #: INCMGA 0012-104
• Status: Completed
• Phase: Phase 1
• Start date: July 22, 2019
• Est. completion date: December 14, 2021

Study information

• Verified date: February 2022
• Source: Incyte Corporation
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 18
• Est. completion date: December 14, 2021
• Est. primary completion date: December 14, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Advanced Solid Tumors
• Metastatic Solid Tumors
• Neoplasms

Intervention

Drug:
• Retifanlimab
Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.
• INCB001158
Part 1: INCB001158 75 or 100 mg twice daily administered orally.
• Retifanlimab + INCB001158
Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 .

Locations

Country	Name	City	State
Japan	National Cancer Center Hospital	Chuo Ku
Japan	National Cancer Center Hospital East	Kashiwa

Sponsors (1)

Lead Sponsor	Collaborator
Incyte Biosciences Japan GK

Country where clinical trial is conducted

Japan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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	Part 1: Cmax of single-agent INCMGA000012	Maximum observed plasma or serum concentration.	Up to 15 days
Secondary	Part 1: Cmax of single-agent INCB001158	Maximum observed plasma or serum concentration.	Up to 15 days
Secondary	Part 1: Tmax of single-agent INCMGA000012	Time to maximum concentration.	Up to 15 days
Secondary	Part 1: Tmax of single-agent INCB001158	Time to maximum concentration.	Up to 15 days
Secondary	Part 1: Cmin of single-agent INCMGA000012	Minimum observed plasma or serum concentration over the dose interval.	Up to 15 days
Secondary	Part 1: Cmin of single-agent INCB001158	Minimum observed plasma or serum concentration over the dose interval.	Up to 15 days
Secondary	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
Secondary	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
Secondary	Part 1: t½ of single-agent INCMGA000012	Apparent terminal-phase disposition half-life.	Up to 15 days
Secondary	Part 1: t½ of single-agent INCB001158	Apparent terminal-phase disposition half-life.	Up to 15 days
Secondary	Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment	Maximum observed plasma or serum concentration.	Up to 15 days
Secondary	Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment	Time to maximum concentration.	Up to 15 days
Secondary	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
Secondary	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
Secondary	Part 2: t½ of INCMGA00012 and INCB001158 as a combination treatment	Apparent terminal-phase disposition half-life.	Up to 15 days
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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