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

This study is currently recruiting participants.
Verified October 2017 by Incyte Corporation
Sponsor:
ClinicalTrials.gov Identifier:
NCT02903914
First Posted: September 16, 2016
Last Update Posted: November 2, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Information provided by (Responsible Party):
Incyte Corporation
  Purpose
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.

Condition Intervention Phase
Metastatic Cancer Solid Tumors Non-small Cell Lung Cancer Colorectal Cancer Gastric Cancers Renal Cell Carcinoma Squamous Cell Carcinoma of the Head and Neck Bladder Cancer Urothelial Carcinoma Mesothelioma Drug: INCB001158 Drug: Pembrolizumab Phase 1 Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by Incyte Corporation:

Primary Outcome Measures:
  • Safety and Tolerability of INCB001158 as a single agent and in combination with Pembrolizumab: Incidence of Adverse Events [ Time Frame: Every 28 days (single agent INCB001158) or 21 days (INCB001158 in combination with Pembrolizumab) from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
    Evaluation of adverse events (AEs) and changes in laboratory values, vital signs, and physical examinations.


Secondary Outcome Measures:
  • Recommended Phase 2 Dose (RP2D) of INCB001158 [ Time Frame: 12 Weeks ]
    Up to 42 patients with advanced/metastatic solid tumors will be enrolled in Dose Escalation to determine the RP2D of INCB001158 as monotherapy.

  • RP2D of INCB001158 with Pembrolizumab [ Time Frame: 12 Weeks ]
    Up to 42 patients with advanced/metastatic solid tumors will be enrolled in Dose Escalation to determine the RP2D of INCB001158 with Pembrolizumab.

  • Plasma pharmacokinetic (PK) profile of INCB001158 alone and in combination with Pembrolizumab [ Time Frame: 12 Weeks ]
    Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.

  • Anti-tumor Activity of INCB001158 as Monotherapy and in Combination with Pembrolizumab for patients with advanced/metastatic solid tumors [ Time Frame: Until disease progression/study discontinuation up to 24 months ]
    Assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.


Estimated Enrollment: 346
Study Start Date: September 2016
Estimated Study Completion Date: May 2019
Estimated Primary Completion Date: May 2019 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Monotherapy Dose Escalation Solid Tumors
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
Arginase Inhibitor
Other Name: CB-1158
Experimental: INCB001158 as Monotherapy in NSCLC
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
Arginase Inhibitor
Other Name: CB-1158
Experimental: INCB001158 as Monotherapy in CRC
Monotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Experimental: INCB001158 as Monotherapy in Solid Tumors
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
Arginase Inhibitor
Other Name: CB-1158
Experimental: INCB001158 and anti-PD-1 in Combination Dose Escalation
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
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in NSCLC
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
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in Melanoma
Part 3b: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic Melanoma with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in Urothelial Carcinoma
Part 3c: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic Urothelial Carcinoma with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in MSI CRC
Part 3d: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic MSI CRC with disease progression on anti-PD-1 therapy or prolonged stable disease on Pembrolizumab in the immediate prior line of therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in MSS CRC
Part 3e: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic MSS CRC that have received at least 1 prior 5-FU containing therapy and must not have had any prior checkpoint inhibitor therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in Gastric/GE Junction
Part 3f: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic Gastric/GE Junction that have never received prior checkpoint inhibitor therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in SCCHN
Part 3g: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic SCCHN that have never received prior checkpoint inhibitor therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda
Experimental: INCB001158 and anti-PD-1 in Mesothelioma
Part 3h: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic mesothelioma that have received or were unable to receive standard front line standard therapy and have never received prior checkpoint inhibitor therapy.
Drug: INCB001158
Arginase Inhibitor
Other Name: CB-1158
Drug: Pembrolizumab
PD-1 Inhibitor
Other Name: Keytruda

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.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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, 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 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 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
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02903914


Contacts
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com

Locations
United States, Arizona
Honor Health/Pinnacle Oncology Hematology Recruiting
Scottsdale, Arizona, United States, 85258
Contact: Stephanie Althoff         
Principal Investigator: Frank Tsai, MD         
United States, Tennessee
Sarah Cannon Research Institute at Tennessee Oncology Recruiting
Nashville, Tennessee, United States, 37203
Contact: Erin Fisher         
Principal Investigator: Todd Bauer, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77230-1402
Contact: Yan Zhang, MD, PhD         
Principal Investigator: Aung Naing, MD         
START Recruiting
San Antonio, Texas, United States, 78229
Contact: Edwin Blanco-Cepeda, RN         
Sponsors and Collaborators
Incyte Corporation
Investigators
Study Director: Keith W Orford, MD, PhD Calithera Biosciences, Inc
Study Director: Sven Gogov, MD Incyte Corporation
  More Information

Responsible Party: Incyte Corporation
ClinicalTrials.gov Identifier: NCT02903914     History of Changes
Other Study ID Numbers: INCB 01158-101
First Submitted: September 9, 2016
First Posted: September 16, 2016
Last Update Posted: November 2, 2017
Last Verified: October 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Keywords provided by Incyte Corporation:
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

Additional relevant MeSH terms:
Carcinoma
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Colorectal Neoplasms
Stomach Neoplasms
Urinary Bladder Neoplasms
Carcinoma, Renal Cell
Mesothelioma
Neoplasm Metastasis
Head and Neck Neoplasms
Carcinoma, Transitional Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Neoplasms, Squamous Cell
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Colonic Diseases
Intestinal Diseases