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

NCT ID: NCT02903914

Last Updated: 2025-08-05

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 260 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-09-14
• Study Completion Date: 2022-08-15

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.

Conditions

Metastatic Cancer; Solid Tumors; Colorectal Cancer (CRC); Gastric Cancer; Head and Neck Cancer; Lung Cancer; Renal Cell Carcinoma (RCC); Bladder Cancer; UC (Urothelial Cancer); Mesothelioma

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

INCB00158 was administered as monotherapy at 50mg twice daily

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).

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

INCB00158 was administered as monotherapy at 75mg twice daily

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).

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

INCB00158 was administered as monotherapy at 100mg twice daily

Monotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC.

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

INCB00158 was administered as monotherapy at 150mg twice daily

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.

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

INCB00158 was administered in combination with pembroluzimab at 50mg twice daily

Monotherapy Part 2d: INCB001158 administered orally at the RP2D in patients with any tumor types in Parts 2a, 2b, or 2c.

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

INCB00158 was administered in combination with pembroluzimab at 75mg twice daily

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).

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

Pembrolizumab

Intervention Type: DRUG

PD-1 Inhibitor

INCB00158 was administered in combination with pembroluzimab at 100mg twice daily

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.

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

Pembrolizumab

Intervention Type: DRUG

PD-1 Inhibitor

INCB001158 50 mg BID in combination with pembrolizumab

Part C: evaluated a reduced dose of INCB001158 50 mg BID in combination with pembrolizumab with patients with moderately impaired renal function.

Group Type: EXPERIMENTAL

INCB001158

Intervention Type: DRUG

Arginase Inhibitor

Pembrolizumab

Intervention Type: DRUG

PD-1 Inhibitor

Interventions

INCB001158

Arginase Inhibitor

Intervention Type: DRUG

Pembrolizumab

PD-1 Inhibitor

Intervention Type: DRUG

Other Intervention Names

CB-1158; Keytruda

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Incyte Corporation

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Emil Kuriakose, MD

Role: STUDY_DIRECTOR

Calithera Biosciences, Inc

Sven Gogov, MD

Role: STUDY_DIRECTOR

Incyte Corporation

Locations

University of South Alabama

Mobile, Alabama, United States

Honor Health/Pinnacle Oncology Hematology

Scottsdale, Arizona, United States

University of Arizona

Tucson, Arizona, United States

Georgetown

Washington D.C., District of Columbia, United States

Johns Hopkins

Baltimore, Maryland, United States

BIDMC

Boston, Massachusetts, United States

DFCI

Boston, Massachusetts, United States

Henry Ford

Detroit, Michigan, United States

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, United States

Vanderbilt

Nashville, Tennessee, United States

MD Anderson

Houston, Texas, United States

MD Anderson

Houston, Texas, United States

START

San Antonio, Texas, United States

Ospedale San Raffaele

Milan, , Italy

Oncologica Azienda Ospedaliera Universitaria Senese

Siena, , Italy

NKI

Amsterdam, , Netherlands

Radboudumc

Nijmegen, , Netherlands

Hospital Universitari Vall d'Hebron

Barcelona, , Spain

Institut Catala d'Oncologia

Barcelona, , Spain

START Madrid-HM CIOCC

Madrid, , Spain

Countries

United States; Italy; Netherlands; Spain

References

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.

Reference Type: DERIVED

PMID: 39886141 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 39462179 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

Mk3475 Keynote 741

Identifier Type: OTHER

Identifier Source: secondary_id

2017-002903-82

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

INCB 01158-101

Identifier Type: -

Identifier Source: org_study_id