Skip to main content
OpenTrials
Completed

NCT Number: NCT02903914

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

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.

Completed

Looking for future studies?

Notify Me

Key information

Conditions

Metastatic Cancer Adenocarcinoma Adenoma Bladder Cancer Carcinoma Carcinoma, Renal Cell Colonic Diseases Colorectal Cancer (CRC) Colorectal Neoplasms Digestive System Diseases Digestive System Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Gastric Cancer Gastrointestinal Diseases Gastrointestinal Neoplasms Head and Neck Cancer Head and Neck Neoplasms Intestinal Diseases Intestinal Neoplasms Kidney Diseases Kidney Neoplasms Lung Cancer Lung Diseases Lung Neoplasms Male Urogenital Diseases Mesothelioma Neoplasm Metastasis Neoplasms Neoplasms by Histologic Type Neoplasms by Site Neoplasms, Glandular and Epithelial Neoplasms, Mesothelial Neoplastic Processes Parkinson Disease 4, Autosomal Dominant Lewy Body Pathologic Processes Pathological Conditions, Signs and Symptoms Rectal Diseases Renal Cell Carcinoma (RCC) Respiratory Tract Diseases Respiratory Tract Neoplasms Solid Tumors Stomach Diseases Stomach Neoplasms Thoracic Neoplasms UC (Urothelial Cancer) Urinary Bladder Diseases Urinary Bladder Neoplasms Urogenital Diseases Urogenital Neoplasms Urologic Diseases Urologic Neoplasms

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1

Primary location

Ospedale San Raffaele, Milan, Italy

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

*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

Treatment and study plan

INCB001158

Drug

Arginase Inhibitor

Other names: CB-1158

Pembrolizumab

Drug

PD-1 Inhibitor

Other names: Keytruda

Primary outcomes

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

    Time frame: up to study completion (up to approximately 3.5 years)

    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.

Secondary outcomes

  1. Recommended Phase 2 Dose (RP2D) of INCB001158

    Time frame: 12 weeks

    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.

  2. RP2D of INCB001158 in Combination With Pembrolizumab

    Time frame: 12 weeks

    INCB001158 was dosed orally BID.

  3. Objective Response Rate (ORR)

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

    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.

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

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

    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.

  5. Duration of Response (DOR)

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

    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.

  6. Progression-free Survival (PFS)

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

    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.

  7. 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

    Cmax was defined as the maximum observed concentration of INCB001158.

  8. 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

    tmax was defined as the time of the maximum observed concentration of INCB001158.

  9. 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

    AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.

  10. 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

    AUC0-inf was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 extrapolated to infinity.

  11. 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

    t1/2 was defined as the half-life of INCB001158.

  12. 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

    CL/F was defined as the apparent oral dose clearance of INCB001158.

  13. Vz/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

    Vz/F was defined as the apparent volume of distribution of INCB001158.

  14. Cmax of INCB001158 Following Multiple Escalating Doses for Part 1A

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    Cmax was defined as the maximum observed concentration of INCB001158.

  15. Tmax of INCB001158 Following Multiple Escalating Doses for Part 1A

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    tmax was defined as the time of the maximum observed concentration of INCB001158.

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

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.

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

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period.

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

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    t1/2 was defined as the half-life of INCB001158.

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

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    CL/F was defined as the apparent oral dose clearance of INCB001158.

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

    Time frame: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose

    Vz/F was defined as the apparent volume of distribution of INCB001158.

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

    Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose

    Cmax was defined as the maximum observed concentration of INCB001158.

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

    Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose

    tmax was defined as the time of the maximum observed concentration of INCB001158.

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

    Time frame: Fasted: Cycle 1 Day 15: predose; 0.5, 1, 2, 4, 6, 8, and 12 hours post-dose. Fed: Cycle 2 Day 8: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose

    AUC was defined as the area under the concentration-time curve of INCB001158.

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

    Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose

    Cmax was defined as the maximum observed concentration of INCB001158.

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

    Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose

    tmax was defined as the time of the maximum observed concentration of INCB001158.

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

    Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose

    AUC0-t was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to time t.

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

    Time frame: Tablet: Cycle 1 Day 15 (Tablet) and Cycle 2 Day 1 (Capsule): predose; 0.5, 1, 2, 4, 6, 8, and 10 hours post-dose

    AUC0-tau was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to the end of the dosing period.

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

    Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.

    Cmax was defined as the Maximum observed concentration of INCB001158.

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

    Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, 8, 12, and 24 (Part 1A only) hours post-dose.

    tmax was defined as the time of the maximum observed concentration of INCB001158.

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

    Time frame: Cycle 1 Day 1: predose; 0.5, 1, 2, 4, 6, and 8 hours post-dose

    AUC0-8h was defined as the area under the concentration-time curve from dosing (time 0) of INCB001158 to 8 hours post-dose.

Sponsors and collaborators

Lead sponsor

Incyte Corporation

Industry

Registry information

Official study title

Safety, Pharmacokinetics, and Pharmacodynamics of Escalating Oral Doses of the Arginase Inhibitor INCB001158 (Formerly Known as CB1158) as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors

Important dates

Study start
2016
Primary completion
2020
Study completion
2022
First posted
Sep 16, 2016
Registry last updated
Aug 5, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Related clinical trials

Published trials that share one or more normalized conditions with this study.