Interventional Study of INCB 99280 With Ipilimumab in Participants With Select Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to characterize the safety, tolerability, PK, and efficacy of INCB 99280 in combination with ipilimumab in participants with select solid tumors.

Official Title
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A Phase 1 Study of INCB099280 in Combination With Ipilimumab in Participants With Select Solid Tumors

Conditions
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Melanoma, Hepatocellular Carcinoma (HCC), Renal Cell Carcinoma (RCC), Microsatellite Instability - High (MSI-H), Mismatch Repair Deficient (dMMR), Colorectal Carcinoma (CRC)

Intervention / Treatment
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* Drug: INCB 99280 with Ipilimumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Prior systemic therapy, diagnoses and disease setting as follows: For Part 1 (dose escalation), and no history of treatment with anti-CTLA-4 or anti-PD-(L)1 therapy and one of the following, Unresectable or metastatic cutaneous melanoma, or Unresectable of metastatic Child-Pugh Class A NDD not eligible for surgical and/or locoregional therapy, or Intermediate or poor-risk advanced clear cell RCC, or MSI-H or dMMR metastatic CRC and able to provide fresh or archival tumor tissue for central confirmation of MSI-H or dMMR. For Part 2 (dose expansion), IO treatment -naïve, e.g., no prior receipt of an anti PD-1, anti-PD-L1 or PD-L1, anti-CTLA-4, GITR, LAG3, TIM3, OX-40, IL-2, 4-1BB or other immune modulator, and have not received prior systemic therapy and one of the following, Unresectable or metastatic Child-Pugh Class A HCC not eligible for surgical and/or locoregional therapy, or Intermediate - or poor-risk advanced clear cell RCC. ECOG performance score of 0 or 1. Life expectancy > 3 months, in the opinion of the investigator. Histologically confirmed solid tumors with measurable disease per RECIST v1.1. Exception: HCC may be diagnoses based on cross-sectional multiphasic imagining using the AASLD criteria. Willingness to avoid pregnancy or fathering children. Exclusion Criteria: Known history of an additional malignancy. Central nervous system (CNS) metastases requiring treatment and/or leptomeningeal disease. Toxicity from prior therapy that has not recovered. Received thoracic radiation within 6 months of the first dose of study treatment. Participation in another interventional clinical study while receiving INCB099280. Impaired cardiac function of clinically significant cardiac disease. History of evidence of interstitial lung disease including non-infections pneumonitis. Presence of gastrointestinal condition that may affect drug absorption Any autoimmune disease requiring systemic treatment in the past 5 years. Diagnosis of immunodeficiency or receiving chronic systemic steroid therapy at a daily dose exceeding 10 mg of prednisone or equivalent Active infection requiring systemic therapy. History of organ transplantation, including allogeneic stem cell transplantation. Receipt of system antibiotics within 28 days of first dose of study treatment. Probiotic usage is prohibited during the screening and throughout the study treatment period. Received a live vaccine within 28 days of planned start of study drug. Laboratory values outside the Protocol-defined ranges. Other protocol-defined Inclusion/Exclusion Criteria may apply.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose Escalation<br>Participants with RCC and MSI-H/dMMR CRC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks Participants with Melanoma and HCC will receive 1 of 2 doses of INCB099280 BID with up to 4 doses of 3 ipilimumab 3 mg/kg Q3 weeks | Drug: INCB 99280 with Ipilimumab<br>* Dose Escalation and expansion of INCB 99280 with Ipilimumab<br>|
| Experimental: Dose Expansion<br>Participants with RCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 1 mg/kg Q3 weeks of ipilimumab Participants with HCC will receive 1 of two doses of INCB099280 BID with up to 4 doses of ipilimumab 3 mg/kg Q3 weeks of ipilimumab | Drug: INCB 99280 with Ipilimumab<br>* Dose Escalation and expansion of INCB 99280 with Ipilimumab<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of DLTs |  | 2 Years | 
| Incidence of TEAEs | Assessed by physical examinations, changes in vital signs and ECGs, and analysis of clinical laboratory samples. | 2 Years | 
| Incidence of TEAEs leading to dose interruption, dose reduction, or discontinuation of either of the study drugs |  | 2 Years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of INCB099280 in plasma |  | 2 Years | 
| Objective response | Defined as having a best overall response of complete response or partial response by investigator assessment per RECIST v1.1. | 2 Years | 
| Disease control | Defined as having a best overall response of complete response or partial response, or stable disease of ≥ 15 weeks after initiation of study treatment, by investigator assessment per RECIST v1.1. | 2 Years | 
| Duration of Response | Defined as the time from the earliest date of CR or PR until the earliest date of disease progression (by investigator assessment per RECIST v1.1) or death due to any cause if occurring sooner than progression. | 2 Years |