A Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat, With or Without Pembrolizumab, in Advanced Solid Tumors

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety and antitumor activity of INCB001158 plus epacadostat, with or without pembrolizumab, in participants with advanced or metastatic solid tumors.

Official Title
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An Open-Label, Multicenter, Nonrandomized, Dose-Escalation, and Tumor-Expansion Phase 1/2 Study to Evaluate the Safety, Tolerability, and Antitumor Activity of INCB001158 Plus Epacadostat (INCB024360), With or Without Pembrolizumab, in Subjects With Advanced Solid Tumors

Conditions
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Solid Tumors

Intervention / Treatment
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* Drug: INCB001158
* Drug: Epacadostat
* Drug: Pembrolizumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: For Phase 1, subjects with histologically or cytologically confirmed advanced or metastatic solid tumors that have failed prior standard therapy (disease progression; subject intolerance is also allowable). For Phase 2, subjects with the following tumor types who meet protocol-defined criteria: advanced or metastatic NSCLC, melanoma, urothelial carcinoma, SCCHN, SCLC, and CRC. Presence of at least 1 measurable lesion by computed tomography or magnetic resonance imaging per RECIST v1.1. Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1. Resolution of all toxicities and any toxic effect(s) of the most recent prior therapy to Grade 1 or less (except alopecia). Subjects with ≤ Grade 2 neuropathy are an exception and may enroll. Adequate renal, hepatic, and hematologic functions per protocol-defined laboratory parameters within ≤ 7 days before treatment initiation. Exclusion Criteria: Participation in any other study in which receipt of an investigational study drug or device occurred within 2 weeks or 5 half-lives (whichever is longer) before first dose. Has received a prior monoclonal antibody within 4 weeks or 5 half-lives (whichever is shorter) before administration of study drug. Prior chemotherapy or targeted small molecule therapy within 2 weeks before administration of study treatment. Prior therapy with an IDO1 or arginase 1 inhibitor. Active autoimmune disease that has required systemic treatment in past 2 years. Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment. Receipt of a live vaccine within 30 days before the first dose of study treatment. Any history of serotonin syndrome after receiving serotonergic drugs. Use of protocol-defined prior/concomitant therapy. Known or suspected defect in the function of the urea cycle. History of gastrointestinal condition that may affect drug absorption.

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: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: INCB001158 + Epacadostat + Pembrolizumab<br> | Drug: INCB001158<br>* Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.<br>Drug: Epacadostat<br>* Epacadostat at the protocol-defined dose administered orally twice daily.<br>* Other names: INCB024360;Drug: Pembrolizumab<br>* Pembrolizumab at the protocol-defined dose administered intravenously every 3 weeks.<br>* Other names: MK-3475;|
| Experimental: INCB001158 + Epacadostat<br> | Drug: INCB001158<br>* Phase 1: INCB001158 administered orally twice daily at the protocol-defined dose. Phase 2: INCB001158 administered orally twice daily at the recommended dose from Phase 1.<br>Drug: Epacadostat<br>* Epacadostat at the protocol-defined dose administered orally twice daily.<br>* Other names: INCB024360;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 1 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a Treatment-emergent Adverse Event (TEAE) | TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment. | Up to approximately 12 months per subject | 
| Phase 2 Only: Objective Response Rate (ORR) of INCB001158 in Combination With Epacadostat ± Pembrolizumab | Defined as percentage of subjects having a complete response (CR) or partial response (PR) based on investigator assessment per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). | Up to approximately 12 months per subject | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Phase 2 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a TEAE | TEAE defined as any adverse event either reported for the first time or worsening of a pre-existing event after first dose of study treatment. | Up to approximately 12 months per subject | 
| Phase 1 Only: ORR With INCB001158 in Combination With Epacadostat ± Pembrolizumab | Defined as percentage of subjects having a CR or PR based on investigator assessment per RECIST v1.1. | Up to approximately 12 months per subject | 
| Disease Control Rate With INCB001158 in Combination With Epacadostat ± Pembrolizumab | Defined as percentage of subjects having CR, PR, or stable disease for at least 56 days based on investigator assessment per RECIST v1.1. | Up to approximately 12 months per subject | 
| Duration of Response With INCB001158 in Combination With Epacadostat ± Pembrolizumab | Defined as the time from earliest date of disease response until the earliest date of disease progression per RECIST v1.1, or death due to any cause, if occurring sooner than progression. | Up to approximately 12 months per subject | 
| Progression-free Survival With INCB001158 in Combination With Epacadostat ± Pembrolizumab | Defined as the time from date of first dose of study treatment until the earliest date of disease progression (based on investigator assessment of per RECIST v1.1) or death due to any cause, if occurring sooner than progression. | Up to approximately 12 months per subject | 
| Plasma Pharmacokinetic Profile of INCB001158 and Epacadostat | Noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158 and epacadostat. | Up to approximately 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-small cell lung cancer (NSCLC), melanoma, urothelial carcinoma, squamous cell carcinoma of the head and neck (SCCHN), small cell lung cancer (SCLC), colorectal cancer (CRC), arginase 1 inhibitor, indoleamine 2,3-dioxygenase 1 inhibitor, programmed death-1 receptor (PD-1) inhibitor