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

• ClinicalTrials.gov Identifier: NCT03910530
• Recruitment Status: Active, not recruiting
• First Posted: April 10, 2019
• Last Update Posted: May 13, 2020
• Sponsor: Incyte Biosciences Japan GK
• Information provided by (Responsible Party): Incyte Corporation ( Incyte Biosciences Japan GK )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Advanced Solid Tumors; Metastatic Solid Tumors	Drug: Retifanlimab; Drug: INCB001158; Drug: Retifanlimab + INCB001158	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1b Study of INCMGA00012 (PD-1 Inhibitor), INCB001158 (Arginase Inhibitor), and the Combination in Japanese Participants With Advanced Solid Tumors
• Actual Study Start Date: July 22, 2019
• Estimated Primary Completion Date: December 31, 2022
• Estimated Study Completion Date: December 31, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: INCMGA00012; Single-agent INCMGA00012.	Drug: Retifanlimab; Part 1: INCMGA00012 500 mg every 4 weeks administered intravenously over 60 minutes.; Other Name: 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 Name: INCMGA00012

Outcome Measures

Primary Outcome Measures :

1. Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCMGA00012 [ Time Frame: 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.
2. Part 1: Number of treatment-emergent adverse events in participants receiving single-agent INCB001158 [ Time Frame: 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.
3. Part 2: Number of treatment-emergent adverse events in participants receiving INCB001158 in combination with INCMGA00012 [ Time Frame: 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 :

1. Part 1: Cmax of single-agent INCMGA000012 [ Time Frame: Up to 15 days ]
   Maximum observed plasma or serum concentration.
2. Part 1: Cmax of single-agent INCB001158 [ Time Frame: Up to 15 days ]
   Maximum observed plasma or serum concentration.
3. Part 1: Tmax of single-agent INCMGA000012 [ Time Frame: Up to 15 days ]
   Time to maximum concentration.
4. Part 1: Tmax of single-agent INCB001158 [ Time Frame: Up to 15 days ]
   Time to maximum concentration.
5. Part 1: Cmin of single-agent INCMGA000012 [ Time Frame: Up to 15 days ]
   Minimum observed plasma or serum concentration over the dose interval.
6. Part 1: Cmin of single-agent INCB001158 [ Time Frame: Up to 15 days ]
   Minimum observed plasma or serum concentration over the dose interval.
7. Part 1: AUCt of single-agent INCMGA000012 [ Time Frame: Up to 15 days ]
   Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
8. Part 1: AUCt of single-agent INCB001158 [ Time Frame: Up to 15 days ]
   Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
9. Part 1: t½ of single-agent INCMGA000012 [ Time Frame: Up to 15 days ]
   Apparent terminal-phase disposition half-life.
10. Part 1: t½ of single-agent INCB001158 [ Time Frame: Up to 15 days ]
    Apparent terminal-phase disposition half-life.
11. Part 2: Cmax of INCMGA00012 and INCB001158 as a combination treatment [ Time Frame: Up to 15 days ]
    Maximum observed plasma or serum concentration.
12. Part 2: Tmax of INCMGA00012 and INCB001158 as a combination treatment [ Time Frame: Up to 15 days ]
    Time to maximum concentration.
13. Part 2: Cmin of INCMGA00012 and INCB001158 as a combination treatment [ Time Frame: Up to 15 days ]
    Minimum observed plasma or serum concentration over the dose interval.
14. Part 2: AUCt of INCMGA00012 and INCB001158 as a combination treatment [ Time Frame: Up to 15 days ]
    Area under the plasma or serum concentration-time curve from time = 0 to the last measurable concentration at time = t.
15. Part 2: t½ of INCMGA00012 and INCB001158 as a combination treatment [ Time Frame: Up to 15 days ]
    Apparent terminal-phase disposition half-life.
16. Part 1 and Part 2: Overall response rate with single-agent INCMGA00012 [ Time Frame: 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.
17. Part 1 and Part 2: Overall response rate with single-agent INCB001158 [ Time Frame: 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.
18. Part 1 and Part 2: Overall response rate with INCMGA00012 in combination with INCB001158 [ Time Frame: 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.
19. Part 1 and Part 2: Disease control rate with single-agent INCMGA00012 [ Time Frame: Up to 2 years ]
    Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
20. Part 1 and Part 2: Disease control rate with single-agent INCB001158 [ Time Frame: Up to 2 years ]
    Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
21. Part 1 and Part 2: Disease control rate with INCMGA00012 in combination with INCB001158 [ Time Frame: Up to 2 years ]
    Defined as the number of participants maintaining either an overall response rate or stable disease according to RECIST v1.1.
22. Part 1 and Part 2: Duration of response with single-agent INCMGA00012 [ Time Frame: 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.
23. Part 1 and Part 2: Duration of response with single-agent INCB001158 [ Time Frame: 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.
24. Part 1 and Part 2: Duration of response with INCMGA00012 in combination with INCB001158 [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

Japan

National Cancer Center Hospital

Chuo Ku, Japan, 1040045

National Cancer Center Hospital East

Kashiwa, Japan, 277-8577

Sponsors and Collaborators

Incyte Biosciences Japan GK

Investigators

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

More Information

• Responsible Party: Incyte Biosciences Japan GK
• ClinicalTrials.gov Identifier: NCT03910530
• Other Study ID Numbers: INCMGA 0012-104
• First Posted: April 10, 2019
• Last Update Posted: May 13, 2020
• Last Verified: May 2020

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• 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

Keywords provided by Incyte Corporation ( Incyte Biosciences Japan GK ):

Advanced solid tumors; metastatic solid tumors; INCMGA00012; INCB001158; Japan; PD-1 Inhibitor; Arginase Inhibitor

Additional relevant MeSH terms:

Neoplasms