Clinical Trials /

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

NCT02903914

Description:

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.

Related Conditions:
  • Gastric Carcinoma
  • Head and Neck Squamous Cell Carcinoma
  • Malignant Solid Tumor
  • Non-Small Cell Lung Carcinoma
  • Renal Cell Carcinoma
  • Urothelial Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: INCB 01158-101
  • NCT ID: NCT02903914

Conditions

  • 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

Interventions

DrugSynonymsArms
INCB001158CB-1158Monotherapy Dose Escalation Solid Tumors
PembrolizumabKeytrudaINCB001158 and anti-PD-1 in Combination Dose Escalation

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.

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.
    

Trial Arms

NameTypeDescriptionInterventions
Monotherapy Dose Escalation Solid TumorsExperimentalMonotherapy 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).
  • INCB001158
INCB001158 as Monotherapy in NSCLCExperimentalMonotherapy 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).
  • INCB001158
INCB001158 as Monotherapy in CRCExperimentalMonotherapy Part 2b: INCB001158 administered orally at the RP2D in patients with advanced/metastatic CRC previously treated with SOC.
  • INCB001158
INCB001158 as Monotherapy in Solid TumorsExperimentalMonotherapy 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.
  • INCB001158
INCB001158 and anti-PD-1 in Combination Dose EscalationExperimentalCombination 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).
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in NSCLCExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in MelanomaExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in Urothelial CarcinomaExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in MSI CRCExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in MSS CRCExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in Gastric/GE JunctionExperimentalPart 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.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in SCCHNExperimentalPart 3g: INCB001158 and Pembrolizumab at the combination RP2D administered in patients with advanced/metastatic SCCHN that have never received prior checkpoint inhibitor therapy.
  • INCB001158
  • Pembrolizumab
INCB001158 and anti-PD-1 in MesotheliomaExperimentalPart 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.
  • INCB001158
  • Pembrolizumab

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

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
Safety Issue:
Description:Evaluation of adverse events (AEs) and changes in laboratory values, vital signs, and physical examinations.

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) of INCB001158
Time Frame:12 Weeks
Safety Issue:
Description:Up to 42 patients with advanced/metastatic solid tumors will be enrolled in Dose Escalation to determine the RP2D of INCB001158 as monotherapy.
Measure:RP2D of INCB001158 with Pembrolizumab
Time Frame:12 Weeks
Safety Issue:
Description:Up to 42 patients with advanced/metastatic solid tumors will be enrolled in Dose Escalation to determine the RP2D of INCB001158 with Pembrolizumab.
Measure:Plasma pharmacokinetic (PK) profile of INCB001158 alone and in combination with Pembrolizumab
Time Frame:12 Weeks
Safety Issue:
Description:Non-compartmental method of analysis will be used to analyze the plasma concentrations of INCB001158.
Measure: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
Safety Issue:
Description:Assessment of anti-tumor activity per RECIST Criteria (v1.1) and immune-related RECIST (irRECIST) criteria.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Incyte Corporation

Trial 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

Last Updated

October 31, 2017