NCT02903914 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1
Status at capture: COMPLETED
Registry last update: 2025-08-05

This study is an open-label Phase 1/Phase 2 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Number of Participants With Any Treatment-emergent Adverse Event (TEAE)

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outcome · POSTED

Recommended Phase 2 Dose (RP2D) of INCB001158

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outcome · POSTED

RP2D of INCB001158 in Combination With Pembrolizumab

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outcome · POSTED

Objective Response Rate (ORR)

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outcome · POSTED

Percentage of Participants With the Indicated Best Overall Response (BOR)

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outcome · POSTED

Duration of Response (DOR)

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outcome · POSTED

Progression-free Survival (PFS)

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outcome · POSTED

Cmax of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

Tmax of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

t1/2 of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

CL/F of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

Vz/F of INCB001158 Following Single Escalating Doses for Part 1A

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outcome · POSTED

Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

AUC0-t of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

AUC0-tau of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

t1/2 of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

CL/F of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

Vz/F of INCB001158 Following Multiple Escalating Doses for Part 1A

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outcome · POSTED

Cmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food

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outcome · POSTED

Tmax of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food

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outcome · POSTED

AUC of INCB001158 in the Fed and Fasted States Following Multiple Doses for Part 1A to Assess the Effect of Food

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outcome · POSTED

Cmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation

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outcome · POSTED

Tmax of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation

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outcome · POSTED

AUC0-t of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation

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outcome · POSTED

AUC0-tau of INCB001158 for Capsules Versus Tablets for Part 2D to Assess the Effect of Formulation

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outcome · POSTED

Cmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)

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outcome · POSTED

Tmax of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)

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outcome · POSTED

AUC0-8h of INCB001158 in Participants With Renal Impairment (Part 1C) and Normal Renal Function (Part 1A)

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

eligibility Criteria: \*Additional cohort specific criteria may apply Inclusion Criteria: * Must be age 18 or older * Ability to provide written informed consent in accordance with federal, local, and institutional guidelines * Histological or cytological diagnosis of metastatic cancer or locally advanced cancer that is not amenable to local therapy * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1 * Life Expectancy of at least 3 months * Adequate hepatic, renal (moderately impaired renal function in cohort 1c only), cardiac, and hematologic function * Measurable disease by RECISTv1.1 criteria * Resolution of treatment-related toxicities * Willingness to avoid pregnancy or fathering children * Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3a - 3d Exclusion Criteria: * Currently pregnant or lactating * Unable to receive oral medications * Unable to receive oral or IV hydration * Intolerance to prior anti-PD-1/PD-L1 therapy * Prior anti-PD-1 treatment for combination dose expansion cohorts 1c, 3e - 3h * Prior severe hypersensitivity reaction to another monoclonal antibody (mAb) * Any other current or previous malignancy within 3 years except protocol allowed malignancies * Chemotherapy, Tyrosine Kinase Inhibitor therapy, radiation therapy or hormonal therapy within 2 weeks * Immunotherapy or biological therapy, or investigational agent within 3 weeks (Note: some cohort exceptions allow anti-PD-1 therapy) * Active known or suspected exclusionary autoimmune disease * Any condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other systemic immunosuppressive medications within 2 weeks * Concomitant therapy with valproic acid/valproate-containing therapies * Concomitant therapy with allopurinol and other xanthine oxidase inhibitors * History of known risks factors for bowel perforation * Symptomatic ascites or pleural effusion * Major surgery within 28 days before Cycle 1 Day 1 * Active infection requiring within 2 weeks prior to first dose of study drug * Patients who have HIV, Hepatitis B or C * Conditions that could interfere with treatment or protocol-related procedures * Active, non-stable brain metastases or CNS disease * Known deficiencies or suspected defect in the urea cycle * Received live-virus vaccination within 30 days (seasonal flu vaccine allowed if non-live virus) * NSCLC with EGFR or ALK mutation
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Monotherapy Part 1a: INCB001158 administered orally in patients with advanced/metastatic solid tumors. Escalating doses will be explored to determine the recommended phase 2 dose (RP2D).
intervention Names
Drug: INCB001158
label
INCB00158 was administered as monotherapy at 50mg twice daily
type
EXPERIMENTAL
description
Monotherapy Part 2a: INCB001158 administered orally at the RP2D in patients with advanced/metastatic NSCLC (EGFR and Anaplastic Lymphoma Kinase (ALK) negative) previously treated with Standard of Care (SOC).
intervention Names
Drug: INCB001158
label
INCB00158 was administered as monotherapy at 75mg twice daily
type
EXPERIMENTAL
description
Monotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC.
intervention Names
Drug: INCB001158
label
INCB00158 was administered as monotherapy at 100mg twice daily
type
EXPERIMENTAL
description
Monotherapy Part 2c: INCB001158 administered orally at the RP2D in patients with Bladder Cancer, Gastric or Gastroesophageal Junction (GEJ) Cancer, Renal Cell Cancer (RCC), Squamous Cell Carcinoma of the Head and Neck (SCCHN), Urothelial Cell Cancer (UCC), or Melanoma, previously treated with SOC.
intervention Names
Drug: INCB001158
label
INCB00158 was administered as monotherapy at 150mg twice daily
type
EXPERIMENTAL
description
Monotherapy Part 2d: INCB001158 administered orally at the RP2D in patients with any tumor types in Parts 2a, 2b, or 2c.
intervention Names
Drug: INCB001158
label
INCB00158 was administered in combination with pembroluzimab at 50mg twice daily
type
EXPERIMENTAL
description
Combination Part 1b: INCB001158 and Pembrolizumab administered in patients with advanced/metastatic NSCLC, Melanoma, Urothelial Cell Cancer, MSI CRC, MSS CRC, Gastric or Gastroesophageal Junction (GEJ) Cancer, SCCHN and Mesothelioma. Multiple dose levels will be explored to determine the recommended phase 2 dose (RP2D).
intervention Names
Drug: INCB001158
Drug: Pembrolizumab
label
INCB00158 was administered in combination with pembroluzimab at 75mg twice daily
type
EXPERIMENTAL
description
Part 3a: INCB001158 and Pembrolizumab the combination RP2D in patients with advanced/metastatic NSCLC (EGFR and ALK negative) with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy.
intervention Names
Drug: INCB001158
Drug: Pembrolizumab
label
INCB00158 was administered in combination with pembroluzimab at 100mg twice daily
type
EXPERIMENTAL
description
Part C: evaluated a reduced dose of INCB001158 50 mg BID in combination with pembrolizumab with patients with moderately impaired renal function.
intervention Names
Drug: INCB001158
Drug: Pembrolizumab
label
INCB001158 50 mg BID in combination with pembrolizumab
type
EXPERIMENTAL

interventions

arm Group Labels
INCB001158 50 mg BID in combination with pembrolizumab
INCB00158 was administered as monotherapy at 100mg twice daily
INCB00158 was administered as monotherapy at 150mg twice daily
INCB00158 was administered as monotherapy at 50mg twice daily
INCB00158 was administered as monotherapy at 75mg twice daily
INCB00158 was administered in combination with pembroluzimab at 100mg twice daily
INCB00158 was administered in combination with pembroluzimab at 50mg twice daily
INCB00158 was administered in combination with pembroluzimab at 75mg twice daily
description
Arginase Inhibitor
name
INCB001158
other Names
CB-1158
type
DRUG
arm Group Labels
INCB001158 50 mg BID in combination with pembrolizumab
INCB00158 was administered in combination with pembroluzimab at 100mg twice daily
INCB00158 was administered in combination with pembroluzimab at 75mg twice daily
description
PD-1 Inhibitor
name
Pembrolizumab
other Names
Keytruda
type
DRUG

Study design

allocation

NON_RANDOMIZED

intervention Model

FACTORIAL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 260
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Number of Participants With Any Treatment-emergent Adverse Event (TEAE)
time Frame
up to study completion (up to approximately 3.5 years)

secondary Outcomes

description
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.
measure
Recommended Phase 2 Dose (RP2D) of INCB001158
time Frame
12 weeks
description
INCB001158 was dosed orally BID.
measure
RP2D of INCB001158 in Combination With Pembrolizumab
time Frame
12 weeks
description
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.
measure
Objective Response Rate (ORR)
time Frame
Until disease progression/study discontinuation (up to approximately 5 years)
description
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.
measure
Percentage of Participants With the Indicated Best Overall Response (BOR)
time Frame
Until disease progression/study discontinuation (up to approximately 5 years)
description
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.
measure
Duration of Response (DOR)
time Frame
Until disease progression/study discontinuation (up to approximately 5 years)
description
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.
measure
Progression-free Survival (PFS)
time Frame
Until disease progression/study discontinuation (up to approximately 5 years)
description
Cmax was defined as the maximum observed concentration of INCB001158.
measure
Cmax of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
description
tmax was defined as the time of the maximum observed concentration of INCB001158.
measure
Tmax of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
description
AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.
measure
AUC0-t of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
description
AUC0-inf was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 extrapolated to infinity.
measure
AUC0-inf of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
description
t1/2 was defined as the half-life of INCB001158.
measure
t1/2 of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose
description
CL/F was defined as the apparent oral dose clearance of INCB001158.
measure
CL/F of INCB001158 Following Single Escalating Doses for Part 1A
time Frame
Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 hours post-dose

Full study description

brief Summary: This study is an open-label Phase 1/Phase 2 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors.
detailed Description: This study is an open-label Phase 1 evaluation of INCB001158 as a single agent and in combination with immune checkpoint therapy in patients with advanced/metastatic solid tumors. Single Agent INCB001158: Patients with advanced/metastatic solid tumors will be enrolled into escalating monotherapy dose cohorts to determine the Recommended Phase 2 Dose (RP2D) of INCB001158. Additional patients with NSCLC, Colorectal Cancer (CRC), and other tumors including SCCHN, RCC, Gastric, Bladder and Melanoma will be enrolled at the single agent RP2D. Combination Treatment: Patients with advanced/metastatic NSCLC, Melanoma, Urothelial, Microsatellite Instability (MSI)/ Microsatellite Stable (MSS) CRC, Gastric, SCCHN and Mesothelioma will be enrolled into separate cohorts of combination therapy (INCB001158 and Pembrolizumab) to determine the RP2D. In the dose expansion phase, additional patients with NSCLC, Melanoma, Urothelial, MSI/MSS CRC, Gastric, SCCHN and Mesothelioma will be treated with the combination of INCB001158 and Pembrolizumab at the RP2D. All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

Source references

references

citation
Naing A, Papadopoulos KP, Pishvaian MJ, Rahma O, Hanna GJ, Garralda E, Saavedra O, Gogov S, Kallender H, Cheng L, Smith M, Chen X, Kuriakose E, Bauer T. First-in-human phase 1 study of the arginase inhibitor INCB001158 alone or combined with pembrolizumab in patients with advanced or metastatic solid tumours. BMJ Oncol. 2024 May 9;3(1):e000249. doi: 10.1136/bmjonc-2023-000249. eCollection 2024.
pmid
39886141
type
DERIVED
citation
Aden D, Sureka N, Zaheer S, Chaurasia JK, Zaheer S. Metabolic Reprogramming in Cancer: Implications for Immunosuppressive Microenvironment. Immunology. 2025 Jan;174(1):30-72. doi: 10.1111/imm.13871. Epub 2024 Oct 27.
pmid
39462179
type
DERIVED

Source notices and limitations

Discovery and provenance

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Preserved source evidence · Not medical advice