Trial Outcomes & Findings for Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors (NCT NCT02903914)

Last Updated: 2025-08-05

Results Overview

An adverse event (AE) was defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurred after a participant provided informed consent. Abnormal laboratory values or test results occurring after informed consent constituted AEs only if they induced clinical signs or symptoms, were considered clinically meaningful, required therapy (e.g., hematologic abnormality that required transfusion), or required changes in the study treatment(s). A TEAE was defined as any adverse event that started or worsened after the first dose of study drug.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

260 participants

Primary outcome timeframe

up to study completion (up to approximately 3.5 years)

Results posted on

2025-08-05

Participant Flow

This global study (United States, Spain, and Italy) consisted of 3 parts: Part 1 was dose-escalation using a 3 + 3 design to determine the RP2D of INCB001158 as monotherapy (Part 1a) and in combination with pembrolizumab (Parts 1b and 1c); Part 2 and Part 3 consisted of tumor expansion cohorts to determine whether INCB001158 as monotherapy (Part 2) or in combination with pembrolizumab (Part 3) had sufficient antitumor activity and further evaluated the safety and tolerability of the RP2D.

260 enrolled participants: 107 in the Part 1a and Part 2 monotherapy groups; 147 in the Part 1b and Part 3 combination therapy groups; and 6 in Part 1c. Disposition data have been reported by dose level; efficacy data have been reported by tumor type, regardless of dose received. One Part 3 participant scheduled to receive INCB001158 100 mg actually received 75 mg; they were included in the Part 1b 75 mg arm for disposition analysis and in the Part 1c and Part 3 100 mg arm for efficacy analysis.

Participant milestones

Participant milestones
Measure	Part 1A: INCB001158 50 mg INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A and Part 2: INCB001158 100 mg INCB001158 was administered orally at 100 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.
Overall Study STARTED	8	7	85	7	10	14	123	6
Overall Study COMPLETED	0	0	0	0	0	0	0	0
Overall Study NOT COMPLETED	8	7	85	7	10	14	123	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Part 1A: INCB001158 50 mg INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A and Part 2: INCB001158 100 mg INCB001158 was administered orally at 100 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.
Overall Study Adverse Event	0	0	1	0	0	0	2	0
Overall Study Withdrawal by Subject	3	1	28	0	1	2	12	0
Overall Study Progressive Disease	1	0	4	0	0	0	2	0
Overall Study Death	0	0	9	0	1	3	24	2
Overall Study Lost to Follow-up	0	1	0	0	2	0	1	0
Overall Study Physician Decision	0	0	1	0	0	0	1	0
Overall Study Symptomatic Deterioration	0	0	1	0	0	0	0	0
Overall Study New Cancer Therapy	2	2	21	4	3	6	56	3
Overall Study Didn't Return to Site	1	0	1	1	0	0	2	0
Overall Study Entered/Referred to Hospice Care	1	1	8	0	0	0	4	0
Overall Study Follow-up Did Not Occur	0	1	1	0	2	0	8	0
Overall Study Systemic Treatment Options Necessary	0	1	0	0	0	0	0	0
Overall Study Consented to/Considered Other Clinical Study	0	0	2	0	0	2	0	0
Overall Study Clinical Disease Progression	0	0	2	0	0	0	0	0
Overall Study Completed Follow-up Period	0	0	6	2	1	0	9	1
Overall Study Taken off Treatment per Protocol	0	0	0	0	0	1	0	0
Overall Study Refused Further Treatment/Contact	0	0	0	0	0	0	1	0
Overall Study Discontinued per Sponsor/Participant Agreement	0	0	0	0	0	0	1	0

Baseline Characteristics

Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Part 1A: INCB001158 50 mg n=8 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg n=7 Participants INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A and Part 2: INCB001158 100 mg n=85 Participants INCB001158 was administered orally at 100 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg n=7 Participants INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab n=14 Participants INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab n=123 Participants INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab n=6 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Total n=260 Participants Total of all reporting groups
Age, Continuous	56.5 years STANDARD_DEVIATION 3.96 • n=5 Participants	61.7 years STANDARD_DEVIATION 6.10 • n=7 Participants	61.4 years STANDARD_DEVIATION 10.42 • n=5 Participants	67.0 years STANDARD_DEVIATION 8.12 • n=4 Participants	58.7 years STANDARD_DEVIATION 11.64 • n=21 Participants	62.8 years STANDARD_DEVIATION 10.81 • n=10 Participants	59.7 years STANDARD_DEVIATION 11.94 • n=115 Participants	73.3 years STANDARD_DEVIATION 7.69 • n=24 Participants	60.9 years STANDARD_DEVIATION 10.9 • n=42 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	39 Participants n=5 Participants	4 Participants n=4 Participants	6 Participants n=21 Participants	3 Participants n=10 Participants	43 Participants n=115 Participants	3 Participants n=24 Participants	109 Participants n=42 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	1 Participants n=7 Participants	46 Participants n=5 Participants	3 Participants n=4 Participants	4 Participants n=21 Participants	11 Participants n=10 Participants	80 Participants n=115 Participants	3 Participants n=24 Participants	151 Participants n=42 Participants
Race/Ethnicity, Customized White or Causasian	5 Participants n=5 Participants	7 Participants n=7 Participants	70 Participants n=5 Participants	6 Participants n=4 Participants	9 Participants n=21 Participants	13 Participants n=10 Participants	109 Participants n=115 Participants	5 Participants n=24 Participants	224 Participants n=42 Participants
Race/Ethnicity, Customized Black or African American	2 Participants n=5 Participants	0 Participants n=7 Participants	11 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	3 Participants n=115 Participants	1 Participants n=24 Participants	18 Participants n=42 Participants
Race/Ethnicity, Customized Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	3 Participants n=5 Participants	0 Participants n=4 Participants	1 Participants n=21 Participants	1 Participants n=10 Participants	4 Participants n=115 Participants	0 Participants n=24 Participants	10 Participants n=42 Participants
Race/Ethnicity, Customized American Indican/Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Native Hawaiian or Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	0 Participants n=115 Participants	0 Participants n=24 Participants	0 Participants n=42 Participants
Race/Ethnicity, Customized Captured as "Other" in Database	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	6 Participants n=115 Participants	0 Participants n=24 Participants	7 Participants n=42 Participants
Race/Ethnicity, Customized Missing	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	2 Participants n=115 Participants	0 Participants n=24 Participants	2 Participants n=42 Participants
Race/Ethnicity, Customized Hispanic or Latino	2 Participants n=5 Participants	1 Participants n=7 Participants	10 Participants n=5 Participants	1 Participants n=4 Participants	0 Participants n=21 Participants	0 Participants n=10 Participants	7 Participants n=115 Participants	0 Participants n=24 Participants	21 Participants n=42 Participants
Race/Ethnicity, Customized Not Hispanic or Latino	6 Participants n=5 Participants	6 Participants n=7 Participants	75 Participants n=5 Participants	6 Participants n=4 Participants	10 Participants n=21 Participants	14 Participants n=10 Participants	114 Participants n=115 Participants	6 Participants n=24 Participants	237 Participants n=42 Participants

PRIMARY outcome

Timeframe: up to study completion (up to approximately 3.5 years)

Population: Safety Population: all participants who received at least 1 dose of INCB001158 or pembrolizumab. Data collected through study completion have been reported.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg n=8 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg n=7 Participants INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg n=85 Participants INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg n=7 Participants INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab n=14 Participants INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab n=123 Participants INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab n=6 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)	7 Participants	7 Participants	81 Participants	7 Participants	10 Participants	13 Participants	123 Participants	6 Participants	—

SECONDARY outcome

Timeframe: 12 weeks

Population: Safety Population

The RP2D was determined by a traditional 3+3 dose-escalation design of single-agent INCB001158 in participants with advanced/metastatic solid tumors at doses of 50, 75, 100, or 150 mg.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg n=28 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
Recommended Phase 2 Dose (RP2D) of INCB001158	100 milligrams	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: 12 weeks

Population: Safety Population

INCB001158 was dosed orally BID.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg n=33 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
RP2D of INCB001158 in Combination With Pembrolizumab	100 milligrams	—	—	—	—	—	—	—	—

SECONDARY outcome

Timeframe: Until disease progression/study discontinuation (up to approximately 5 years)

Population: Response Efficacy Evaluable Population (REEP): received ≥1 dose of INCB001158 or pembrolizumab, completed a Baseline scan, and met ≥1 protocol-defined criteria. Part 1c participants had renal impairment and received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function.

ORR was defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) as the percentage of participants with a confirmed best overall response of complete response (CR) or partial response (PR) at any post-Baseline visits prior to first disease progression and alternative cancer therapy use. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma was evaluated using modified RECIST criteria. Confidence intervals were calculated based on the exact method for binomial distributions (Clopper Pearson). Two participants evaluable for PFS were not evaluable for response.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg n=6 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg n=7 Participants INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg n=6 Participants INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg n=6 Participants INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab n=13 Participants INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab n=73 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab n=118 Participants INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
Objective Response Rate (ORR)	0.0 percentage of participants Interval 0.0 to 45.9	0.0 percentage of participants Interval 0.0 to 41.0	0.0 percentage of participants Interval 0.0 to 45.9	0.0 percentage of participants Interval 0.0 to 45.9	10.0 percentage of participants Interval 0.3 to 44.5	7.7 percentage of participants Interval 0.2 to 36.0	0.0 percentage of participants Interval 0.0 to 30.8	1.4 percentage of participants Interval 0.0 to 7.4	11.0 percentage of participants Interval 6.0 to 18.1

SECONDARY outcome

Timeframe: Until disease progression/study discontinuation (up to approximately 5 years)

Population: REEP. Participants enrolled in Part 1c had renal impairment. These participants received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function. Two participants evaluable for PFS were not evaluable for response.

BOR was evaluated per RECIST v1.1. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 mm. PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Stable disease (SD): no change in target lesions to qualify for CR, PR, or progressive disease (PD). PD: progression of a target or non-target lesion or presence of a new lesion. Missing: participant had a missing BOR because there were no post-Baseline tumor assessments. Pleural mesothelioma was evaluated using modified RECIST criteria.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg n=6 Participants INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg n=7 Participants INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg n=6 Participants INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg n=6 Participants INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab n=13 Participants INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab n=10 Participants INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab n=73 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab n=118 Participants INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
Percentage of Participants With the Indicated Best Overall Response (BOR) Complete Response	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	1.7 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Partial Response	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	10.0 percentage of participants	7.7 percentage of participants	0.0 percentage of participants	1.4 percentage of participants	9.3 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Stable Disease	33.3 percentage of participants	0.0 percentage of participants	16.7 percentage of participants	33.3 percentage of participants	10.0 percentage of participants	38.5 percentage of participants	20.0 percentage of participants	30.1 percentage of participants	36.4 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Progressive Disease	66.7 percentage of participants	85.7 percentage of participants	83.3 percentage of participants	66.7 percentage of participants	70.0 percentage of participants	46.2 percentage of participants	80.0 percentage of participants	50.7 percentage of participants	44.9 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Not Evaluable	0.0 percentage of participants	14.3 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	4.1 percentage of participants	4.2 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Not Assessed	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants
Percentage of Participants With the Indicated Best Overall Response (BOR) Missing	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	0.0 percentage of participants	10.0 percentage of participants	7.7 percentage of participants	0.0 percentage of participants	13.7 percentage of participants	3.4 percentage of participants

SECONDARY outcome

Timeframe: Until disease progression/study discontinuation (up to approximately 5 years)

Population: REEP. Only participants with CR or PR were analyzed, and only cohorts with ≥5 objective responders were analyzed. Part 1c participants had renal impairment and received INCB001158 50 mg + pembrolizumab (half the RP2D of INCB001158). It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function. Two participants evaluable for PFS were not evaluable for response.

DOR was defined as the number of months from the date of the first documentation of an objective response (CR or PR per RECIST v1.1) to the date of the first documentation of disease progression or death, whichever occurred first. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Pleural mesothelioma will be evaluated using modified RECIST criteria. Kaplan-Meier (KM) product-limit estimates with a log-log transformation were used for 95% confidence interval calculation.

Outcome measures

Outcome measures
Measure	Part 1A: INCB001158 50 mg INCB001158 was administered orally at 50 milligrams (mg) twice daily (BID) in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 75 mg INCB001158 was administered orally at 75 mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 100 mg INCB001158 administered orally at 100mg BID in participants with advanced/metastatic solid tumors.	Part 1A: INCB001158 150 mg INCB001158 was administered orally at 150 mg BID in participants with advanced/metastatic solid tumors.	Part 1B: INCB001158 50 mg + Pembrolizumab n=1 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg intravenously (IV) every 3 weeks (Q3W).	Part 1B: INCB001158 75 mg + Pembrolizumab n=1 Participants INCB001158 was administered orally at 75 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1B and Part 3: INCB001158 100 mg + Pembrolizumab INCB001158 was administered orally at 100 mg BID in combination with pembrolizumab at 200 mg IV Q3W.	Part 1C: INCB001158 50 mg + Pembrolizumab n=1 Participants INCB001158 was administered orally at 50 mg BID in combination with pembrolizumab at 200 mg IV Q3W to participants with moderately impaired renal function.	Part 1c and Part 3: INCB001158 100 mg + Pembrolizumab n=5 Participants INCB001158 was administered orally at 100 mg BID (50 mg BID for Part 1c renally impaired participants) in combination with pembrolizumab at 200 mg IV Q3W.
Duration of Response (DOR)	—	—	—	—	NA months The KM estimation method on a sample of \<5 responders is not valid because too few participants were responders.	NA months The KM estimation method on a sample of \<5 responders is not valid because too few participants were responders.	—	NA months The KM estimation method on a sample of \<5 responders is not valid because too few participants were responders.	12.4 months Interval 4.2 to The upper limit of the confidence interval was not estimable because too few participants had disease progression or died.

SECONDARY outcome

Timeframe: Until disease progression/study discontinuation (up to approximately 5 years)

Population: PFS Efficacy Evaluable Population (Full Analysis Set): all participants who received at least 1 dose of INCB001158 or pembrolizumab. One participant was to be treated with INCB001158 100 mg + pembrolizumab but actually received INCB001158 75 mg + pembrolizumab. For PFS analysis, this participant was analyzed in their planned treatment group (INCB001158 100 mg + pembrolizumab) rather than in the actual treatment group.

PFS was defined as the length of time between the date of the first dose and the earlier of death or progressive disease as assessed by RECIST v1.1. Pleural mesothelioma was evaluated using modified RECIST criteria. Participants enrolled in Part 1c had renal impairment. These participants received INCB001158 50 mg + pembrolizumab, which was half the recommended Phase 2 dose of INCB001158. In renally impaired participants, the 50 mg dose has comparable exposure to 100 mg in participants with normal renal function. It was pre-specified to combine Part 1c and Part 3 participants for efficacy analysis based on planned comparable dosing according to renal function.