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

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

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 Overview

• Status: Completed
• Conditions: Advanced Solid Tumors; Metastatic Solid Tumors
• Intervention / Treatment: Drug: Retifanlimab; Drug: INCB001158; Drug: Retifanlimab + INCB001158

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Contacts and Locations

Study Locations

• Japan
  • Chuo Ku, Japan, 1040045
    • National Cancer Center Hospital
  • Kashiwa, Japan, 277-8577
    • National Cancer Center Hospital East

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: INCMGA00012; Single-agent INCMGA00012.	Drug: Retifanlimab; Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.; Other Names: INCMGA00012
EXPERIMENTAL: INCB001158 75 mg; Single-agent INCB001158.	Drug: INCB001158; Part 1: INCB001158 75 or 100 mg twice daily administered orally.
EXPERIMENTAL: INCB001158 100 mg; Single-agent INCB001158.	Drug: INCB001158; Part 1: INCB001158 75 or 100 mg twice daily administered orally.
EXPERIMENTAL: INCMGA00012 + INCB001158; Combination of INCMGA00012 and INCB001158.	Drug: Retifanlimab + INCB001158; Part 2: INCB001158 at the recommended Phase 2 dose selected from Part 1 in combination with INCMGA00012 .; Other Names: INCMGA00012

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Incyte Biosciences Japan GK
• Investigators: Study Director: Eiji Ueda, MD, PhD, MBA, Incyte Biosciences Japan GK

Study record dates

Study Major Dates

• Study Start (ACTUAL): July 22, 2019
• Primary Completion (ACTUAL): December 14, 2021
• Study Completion (ACTUAL): December 14, 2021

Study Registration Dates

• First Submitted: April 9, 2019
• First Submitted That Met QC Criteria: April 9, 2019
• First Posted (ACTUAL): April 10, 2019

Study Record Updates

• Last Update Posted (ACTUAL): February 25, 2022
• Last Update Submitted That Met QC Criteria: February 24, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: metastatic solid tumors; Japan; Advanced solid tumors; INCMGA00012; PD-1 Inhibitor; INCB001158; Arginase Inhibitor
• Additional Relevant MeSH Terms: Neoplasms
• Other Study ID Numbers: INCMGA 0012-104

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes