A Study to Evaluate INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive

Study Overview
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Brief Summary
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This study is being conducted to determine the safety, tolerability, and preliminary efficacy of INCB099280 in participants with advanced solid tumors.

Official Title
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A Phase 2 Study Evaluating INCB099280 in Participants With Select Solid Tumors Who Are Immune Checkpoint Inhibitor Naive

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: INCB099280


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunotherapy naive and without access to approved and/or available immune checkpoint inhibitor (ICI) therapy. Measurable disease per RECIST v1.1. One of the following disease settings: Unresectable or metastatic Child-Pugh Class A hepatocellular carcinoma (HCC) not eligible for surgical and/or locoregional therapy and have not received prior systemic therapy or had disease progression following primary therapy. Unresectable or metastatic cutaneous melanoma and have not received more than 1 previous systemic therapy for advanced disease. Unresectable Stage III PD-L1-positive (TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay) non-small cell lung cancer (NSCLC) without actionable molecular biomarkers and have not received prior systemic therapy and where chemoradiation is contraindicated; in addition, able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression. Stage IV PD-L1-positive (TPS ≥ 50% using the Dako PD-L1 IHC 22C3 assay) NSCLC without actionable molecular biomarkers and have not received prior systemic therapy; in addition, able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression. Relapsed or Stage IV clear cell renal cell carcinoma (RCC) after having received 1 prior systemic therapy for relapsed or Stage IV disease. Cisplatin-ineligible, locally advanced or Stage IV urothelial cancer (UC) and have not received prior systemic therapy for locally advanced or Stage IV UC and able to provide fresh or archival tumor tissue for central confirmation of PD-L1 expression using the Dako PD-L1 IHC 22C3 assay. Advanced or metastatic microsatellite instability high (MSI-H) or deficient mismatch repair (dMMR) (as determined by an approved assay) solid tumors and able to provide fresh or archival tumor tissue for central confirmation of MSI-H or dMMR. Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1. Life expectancy > 3 months. 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. Prior receipt of an PD-1, anti-PD-L1, or anti-PD-L2 agent or treatment with an immune modulator (eg, CTLA-4, GITR, LAG3, TIM3, OX40, ICOS, IL-2, 4-1BB, CAR-T cell). 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 or clinically significant cardiac disease. History or evidence of interstitial lung disease including noninfectious pneumonitis. Presence of gastrointestinal conditions 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 systemic antibiotics within 28 days of first dose of study treatment. Probiotic usage is prohibited during screening and throughout the study treatment period. Received a live vaccine within 28 days of the 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: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study consists of 2 parts. In Part 1, participants with 6 different tumor types will be randomized 1:1:1 to INCB099280 Dose 1, INCB099280 Dose 2, or INCB099280 Dose 3 twice daily (BID). At the end of Part 1, an integrated analysis will be performed to select a dose. Once a dose is selected, Part 2 will proceed to complete enrollment for each of the 6 disease-specific cohorts at the selected dose.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1: INCB099280 Dose 1<br>Participants will receive INCB099280 dose 1 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>|
| Experimental: Part 1: INCB099280 Dose 2<br>Participants will receive INCB099280 dose 2 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>|
| Experimental: Part 1: INCB099280 Dose 3<br>Participants will receive INCB099280 dose 3 twice daily (BID) for up to 2 years | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>|
| Experimental: Part 2: INCB099280 Dose selected from Part 1<br>Participants will receive INCB099280 dose selected from Part 1 twice daily (BID) for up to 2 years. | Drug: INCB099280<br>* Administered as specified in the treatment arm description<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Objective response rate (ORR) | Defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR), as determined by investigator radiographic disease assessment according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. | Up to 2 years | 
| Number of participants with Treatment-emergent Adverse Events (TEAEs) | 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 90 days after the last dose of study drug or until the start of new anticancer therapy, whichever occurs first. | Up to 2 years 3 months | 
| Number of participants with TEAEs leading to dose modification or discontinuation | Number of participants with TEAEs leading to dose modification or discontinuation. | Up to 2 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Disease Control Rate (DCR) | Defined as the percentage of participants with the best overall response of CR or PR, or stable disease (SD), after a minimum of 15 weeks following the initiation of study treatment by investigator assessment per RECIST v1.1. | Up to 2 years | 
| Duration Of Response (DOR) | Defined as the time from the earliest date of CR or PR until the earliest date of disease progression, as determined by investigator radiographic disease assessment according to RECIST v1.1, or death due to any cause if occurring sooner than progression. | Up to 2 years | 
| INCB099280 pharmacokinetic (PK) in Plasma | INCB099280 concentration in plasma | Pre dose and 1, 2 and 6 hours post dose on Cycle 1 Day 1 and Cycle 2 Day 1. Pre dose every other cycle until Cycle 11 Day 1 (Cycle 3 Day 1, Cycle 5 Day 1, Cycle 7 Day 1, Cycle 9 Day 1 and Cycle 11 Day 1) (each cycle is 28 days) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Advanced Solid Tumor, Hepatocellular Carcinoma, Cutaneous Melanoma, PD-L1-positive NSCLC, Non-small Cell Lung Cancer, Renal Cell Carcinoma, Urothelial Cancer, MSI-H/dMMR Tumors