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

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

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.

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.