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Trial record 3 of 3 for:    incb01158

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

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ClinicalTrials.gov Identifier: NCT02903914
Recruitment Status : Recruiting
First Posted : September 16, 2016
Last Update Posted : March 27, 2018
Sponsor:
Information provided by (Responsible Party):
Incyte Corporation

September 9, 2016
September 16, 2016
March 27, 2018
September 2016
May 2019   (Final data collection date for primary outcome measure)
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.
Safety and Tolerability of CB-1158 as a single agent and in combination with nivolumab: Incidence of Adverse Events [ Time Frame: Every 28 days 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
Complete list of historical versions of study NCT02903914 on ClinicalTrials.gov Archive Site
  • 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.
  • Recommended Phase 2 Dose (RP2D) of CB-1158 [ Time Frame: 12 Weeks ]
    Up to 30 patients with solid tumors will be enrolled in Dose Escalation to determine the RP2D of CB-1158 as monotherapy.
  • RP2D of CB-1158 with Nivolumab [ Time Frame: 12 Weeks ]
    Up to 24 patients with solid tumors will be enrolled in Dose Escalation to determine the RP2D of CB-1158 with Nivolumab
  • Maximum plasma concentration of CB-1158 [ Time Frame: Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months ]
    Non-compartmental method of analysis will be used to analyze the plasma concentrations of CB-1158
Not Provided
Not Provided
 
Arginase Inhibitor INCB001158 as a Single Agent and in Combination With Immune Checkpoint Therapy in Patients With Advanced/Metastatic Solid Tumors
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
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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Intervention Model: Factorial Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
  • 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
  • Drug: INCB001158
    Arginase Inhibitor
    Other Name: CB-1158
  • Drug: Pembrolizumab
    PD-1 Inhibitor
    Other Name: Keytruda
  • 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).
    Intervention: Drug: INCB001158
  • 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).
    Intervention: Drug: INCB001158
  • 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.
    Intervention: Drug: INCB001158
  • 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.
    Intervention: Drug: INCB001158
  • 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).
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
  • 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.
    Interventions:
    • Drug: INCB001158
    • Drug: Pembrolizumab
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
346
236
May 2019
May 2019   (Final data collection date for primary outcome measure)

*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
Sexes Eligible for Study: All
18 Years and older   (Adult, Older Adult)
No
Contact: Incyte Corporation Call Center (US) 1.855.463.3463 medinfo@incyte.com
United States
 
 
NCT02903914
INCB 01158-101
No
Not Provided
Plan to Share IPD: No
Incyte Corporation
Incyte Corporation
Not Provided
Study Director: Keith W Orford, MD, PhD Calithera Biosciences, Inc
Study Director: Sven Gogov, MD Incyte Corporation
Incyte Corporation
March 2018

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP