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

NCT02903914 | Completed Phase 1 Results FDA Drug

• 3 other identifiers: INCB 01158-101Mk3475 Keynote 7412017-002903-82
• Study Type: interventional
• Target: 260
• Locations: 4 countries
• Sites: 20

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.

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

Keywords

Immuno-Oncology; Checkpoint Inhibitors; Tumor Metabolism; Programmed cell death protein-1 (PD-1) inhibitor; Programmed death ligand 1 (PD-L1) inhibitor; Solid Tumors; RCC; MEL; NSCLC; Arginase; Arginase Inhibitor; INCB001158 (CB-1158); SCCHN; GEJ; Immune Therapy

Outcome Measures

Primary Outcomes (1)

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

  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.

  up to study completion (up to approximately 3.5 years)

Secondary Outcomes (30)

• Recommended Phase 2 Dose (RP2D) of INCB001158

  12 weeks

• RP2D of INCB001158 in Combination With Pembrolizumab

  12 weeks

• Objective Response Rate (ORR)

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

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

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

• Duration of Response (DOR)

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

Study Arms (8)

INCB00158 was administered as monotherapy at 50mg twice daily

EXPERIMENTAL

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).

Drug: INCB001158

INCB00158 was administered as monotherapy at 75mg twice daily

EXPERIMENTAL

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).

Drug: INCB001158

INCB00158 was administered as monotherapy at 100mg twice daily

EXPERIMENTAL

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

Drug: INCB001158

INCB00158 was administered as monotherapy at 150mg twice daily

EXPERIMENTAL

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.

Drug: INCB001158

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

EXPERIMENTAL

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

Drug: INCB001158

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

EXPERIMENTAL

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).

Drug: INCB001158; Drug: Pembrolizumab

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

EXPERIMENTAL

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.

Drug: INCB001158; Drug: Pembrolizumab

INCB001158 50 mg BID in combination with pembrolizumab

EXPERIMENTAL

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

Drug: INCB001158; Drug: Pembrolizumab

Interventions

INCB001158 DRUG

Arginase Inhibitor

Also known as: CB-1158

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

Pembrolizumab DRUG

PD-1 Inhibitor

Also known as: Keytruda

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Incyte Corporation: lead

Study Sites (20)

University of South Alabama

Mobile, Alabama, 36604, United States

Location

Honor Health/Pinnacle Oncology Hematology

Scottsdale, Arizona, 85258, United States

Location

University of Arizona

Tucson, Arizona, 85719, United States

Location

Georgetown

Washington D.C., District of Columbia, 20007, United States

Location

Johns Hopkins

Baltimore, Maryland, 21287, United States

Location

BIDMC

Boston, Massachusetts, 02215, United States

Location

DFCI

Boston, Massachusetts, 02215, United States

Location

Henry Ford

Detroit, Michigan, 48202, United States

Location

Sarah Cannon Research Institute at Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Vanderbilt

Nashville, Tennessee, 37232, United States

Location

MD Anderson

Houston, Texas, 77230-1402, United States

Location

MD Anderson

Houston, Texas, 77230, United States

Location

START

San Antonio, Texas, 78229, United States

Location

Ospedale San Raffaele

Milan, 20132, Italy

Location

Oncologica Azienda Ospedaliera Universitaria Senese

Siena, 53100, Italy

Location

NKI

Amsterdam, 1066 CX, Netherlands

Location

Radboudumc

Nijmegen, HP 452, Netherlands

Location

Hospital Universitari Vall d'Hebron

Barcelona, 8035, Spain

Location

Institut Catala d'Oncologia

Barcelona, 8908, Spain

Location

START Madrid-HM CIOCC

Madrid, 28050, Spain

Location

Related Publications (2)

• 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 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Neoplasm Metastasis; Colorectal Neoplasms; Stomach Neoplasms; Head and Neck Neoplasms; Lung Neoplasms; Carcinoma, Renal Cell; Urinary Bladder Neoplasms; Mesothelioma; Parkinson Disease 4, Autosomal Dominant Lewy Body

Interventions

CB-1158; pembrolizumab

Condition Hierarchy (Ancestors)

Neoplastic Processes; Neoplasms; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Stomach Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Diseases; Respiratory Tract Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases; Urinary Bladder Diseases; Adenoma; Neoplasms, Mesothelial

Results Point of Contact

• Title: Incyte Corporation
• Organization: Call Center

medinfo@incyte.com

1-855-463-3463

Study Officials

• Emil Kuriakose, MD

  Calithera Biosciences, Inc

  STUDY DIRECTOR

• Sven Gogov, MD

  Incyte Corporation

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 9, 2016
• First Posted: September 16, 2016
• Study Start: September 14, 2016
• Primary Completion: April 30, 2020
• Study Completion: August 15, 2022
• Last Updated: August 5, 2025
• Results First Posted: September 30, 2021

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (13); ES (3); NL (2); IT (2)