Solid Tumors
Conditions
Keywords
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
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.
Interventions
DRUGINCB001158
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.
DRUGEpacadostat
Epacadostat at the protocol-defined dose administered orally twice daily.
DRUGPembrolizumab
Pembrolizumab at the protocol-defined dose administered intravenously every 3 weeks.
Sponsors
Incyte Corporation
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United States
Participant flow
Recruitment details
The study was conducted at 3 different sites in US. A total of 10 patients were screened and 5 patients enrolled in study.
Pre-assignment details
No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Participants by arm
| Arm | Count |
|---|---|
| INCB001158 50mg BID+ Epacadostat + Pembrolizumab INCB001158 dosed at 50mg BID in combination with epacadostat (100 mg BID) and pembrolizumab (200 mg Q3W) | 0 |
| INCB001158 75 mg BID + Epacadostat + Pembrolizumab INCB001158 dosed at 75mg BID in combination with epacadostat (100 mg BID)and pembrolizumab (200 mg Q3W) | 0 |
| Total | 0 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 3 | 0 |
| Overall Study | Other | 1 | 1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 3 / 4 | 0 / 1 |
| other Total, other adverse events | 4 / 4 | 0 / 1 |
| serious Total, serious adverse events | 3 / 4 | 1 / 1 |
Outcome results
Primary
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.
Time frame: Up to approximately 12 months per subject
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Primary
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).
Time frame: Up to approximately 12 months per subject
Population: Data was not collected as no participants were enrolled in Phase 2 of the study
Secondary
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.
Time frame: Up to approximately 12 months per subject
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Secondary
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.
Time frame: Up to approximately 12 months per subject
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Secondary
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.
Time frame: Up to approximately 12 months per subject
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Secondary
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.
Time frame: Up to approximately 12 months per subject
Population: Data was not collected as no participants were enrolled in Phase 2 of the study
Secondary
Plasma Pharmacokinetic Profile of INCB001158 and Epacadostat
Noncompartmental method of analysis will be used to analyze the plasma concentrations of INCB001158 and epacadostat.
Time frame: Up to approximately 1 month
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2
Secondary
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.
Time frame: Up to approximately 12 months per subject
Population: No patients were analyzed due to insufficient numbers and risk of identifying patient by reporting data on 1 person enrolled in cohort 2