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

Phase 1

Terminated

Conditions: Solid Tumors

Interventions: Drug: INCB001158
Drug: Epacadostat
Drug: Pembrolizumab

Registration Number: NCT03361228

Lead Sponsor: Incyte Corporation

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 5

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
INCB001158 + Epacadostat + Pembrolizumab	Epacadostat	-
INCB001158 + Epacadostat + Pembrolizumab	Pembrolizumab	-
INCB001158 + Epacadostat + Pembrolizumab	INCB001158	-
INCB001158 + Epacadostat	INCB001158	-
INCB001158 + Epacadostat	Epacadostat	-

Primary Outcome Measures

Name	Time	Method
Phase 2 Only: Objective Response Rate (ORR) of INCB001158 in Combination With Epacadostat ± Pembrolizumab	Up to approximately 12 months per subject	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).
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)	Up to approximately 12 months per subject	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.

Secondary Outcome Measures

Name	Time	Method
Phase 2 Only: Safety and Tolerability of INCB001158 in Combination With Epacadostat ± Pembrolizumab as Assessed by Number of Participants With a TEAE	Up to approximately 12 months per subject	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.
Phase 1 Only: ORR With INCB001158 in Combination With Epacadostat ± Pembrolizumab	Up to approximately 12 months per subject	Defined as percentage of subjects having a CR or PR based on investigator assessment per RECIST v1.1.
Disease Control Rate With INCB001158 in Combination With Epacadostat ± Pembrolizumab	Up to approximately 12 months per subject	Defined as percentage of subjects having CR, PR, or stable disease for at least 56 days based on investigator assessment per RECIST v1.1.
Duration of Response With INCB001158 in Combination With Epacadostat ± Pembrolizumab	Up to approximately 12 months per subject	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.
Progression-free Survival With INCB001158 in Combination With Epacadostat ± Pembrolizumab	Up to approximately 12 months per subject	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.
Plasma Pharmacokinetic Profile of INCB001158 and Epacadostat	Up to approximately 1 month	Noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158 and epacadostat.