Clinical Trials /

Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)

NCT02771626

Description:

This study is an open-label Phase 1/ 2 evaluation of CB-839 in combination with nivolumab in patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

Related Conditions:
  • Clear Cell Renal Cell Carcinoma
  • Melanoma
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Completed

Phase:

Phase 1/Phase 2

URL:

https://clinicaltrials.gov/show/NCT02771626

Trial Eligibility

Document

Title

  • Brief Title: Study CB-839 in Combination With Nivolumab in Patients With Melanoma, Clear Cell Renal Cell Carcinoma (ccRCC) and Non-Small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase 1/2 Study of the Safety, Pharmacokinetics, and Pharmacodynamics of the Glutaminase Inhibitor CB-839 in Combination With Nivolumab in Patients With Advanced/Metastatic Melanoma, Renal Cell Carcinoma and Non-Small Cell Lung Cancer

Clinical Trial IDs

  • ORG STUDY ID: CX-839-004
  • NCT ID: NCT02771626

Conditions

  • Clear Cell Renal Cell Carcinoma (ccRCC)
  • Melanoma
  • Non-small Cell Lung Cancer (NSCLC)

Interventions

DrugSynonymsArms
CB-839telaglenastatCB-839 + Nivolumab Dose Escalation
NivolumabOpdivo, BMS-936558CB-839 + Nivolumab Dose Escalation

Purpose

This study is an open-label Phase 1/ 2 evaluation of CB-839 in combination with nivolumab in patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

Detailed Description

      This study is an open-label Phase 1/ 2 evaluation of CB-839 in combination with nivolumab in
      patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung cancer.

      During Phase 1, patients will be enrolled into escalating dose cohorts to determine the
      recommended phase 2 dose (RP2D).

      In Phase 2, patients with clear cell renal cell carcinoma, melanoma, and non-small cell lung
      cancer will be enrolled into separate cohorts.

      All patients will be assessed for safety, pharmacokinetics, biomarkers and tumor response.

Trial Arms

NameTypeDescriptionInterventions
CB-839 + Nivolumab Dose EscalationExperimentalPhase 1: CB-839 administered as oral capsules twice daily in combination with standard dose nivolumab in patients with advanced/metastatic ccRCC, MEL, and NSCLC to select the recommended Phase 2 dose (RP2D).
  • CB-839
  • Nivolumab
Clear Cell RCC Naïve to Checkpoint InhibitorsExperimentalCohort 1: CB-839/nivolumab combination in patients with advanced/metastatic ccRCC who have previously received at least one tyrosine kinase inhibitors (TKI) but are treatment naive to checkpoint modulators programmed death-1/programmed death ligand-1 (PD-1/PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), or any other agent that specifically targets a T-cell checkpoint or co-stimulation pathway.
  • CB-839
  • Nivolumab
Clear Cell RCC Recently Treated with NivolumabExperimentalCohort 2: CB-839/nivolumab combination in patients with advanced/metastatic ccRCC who received nivolumab in most recent treatment line that had documented radiological disease progression OR are currently receiving nivolumab with Stable Disease for at least 24 weeks.
  • CB-839
  • Nivolumab
Clear Cell RCC with Prior PD-1 TherapyExperimentalPhase 2 - Cohort 3: CB-839/ nivolumab combination in patients with advanced/metastatic ccRCC that had documented radiological disease progression while receiving an anti-PD-1/PD-L1 therapy in any prior line of therapy.
  • CB-839
  • Nivolumab
Melanoma with Prior PD-1 TherapyExperimentalCohort 4: CB-839/ nivolumab combination in patients with unresectable or metastatic melanoma that had documented radiological disease progression while receiving an anti-PD-1 therapy in their most recent line of therapy.
  • CB-839
  • Nivolumab
NSCLC with Prior PD-1 TherapyExperimentalCohort 5: CB-839/ nivolumab combination with NSCLC that does not harbor an activating mutation in the epidermal growth factor receptor (EGFR) oncogene and who received nivolumab in most recent treatment line and had documented radiological disease progression OR are currently receiving nivolumab with Stable Disease for at least 24 weeks.
  • CB-839
  • Nivolumab

Eligibility Criteria

        Addition eligibility criteria based on tumor type apply

        Inclusion Criteria:

          -  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 Response Evaluation Criteria in Solid Tumours (RECIST) v1.1
             criteria

          -  Resolution of treatment-related toxicities except alopecia

        Exclusion Criteria:

          -  Unable to receive oral medications

          -  Unable to receive oral or intravenous (IV) hydration

          -  Intolerance to prior anti-PD-1/PD-L1 therapy

          -  Prior severe hypersensitivity reaction to another monoclonal antibody (mAb)

          -  Any other current or previous malignancy within 3 years except protocol allowed
             malignancies

          -  Chemotherapy, TKI 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

          -  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 parenteral antibiotics, antivirals, or antifungals within 2
             weeks prior to first dose of study drug

          -  Patients who have human immunodeficiency virus (HIV), Hepatitis B or C

          -  Conditions that could interfere with treatment or protocol-related procedures

          -  Active and/or untreated central nervous system (CNS) disease or non-stable brain
             metastases
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety and Tolerability of CB-839 and 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
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Recommended Phase 2 Dose (RP2D) of CB-839 in Combination with Nivolumab
Time Frame:12 Weeks
Safety Issue:
Description:A minimum of 9-12 patients with ccRCC, melanoma, or NSCLC will be enrolled in Dose Escalation to determine RP2D.
Measure:Maximum plasma concentration of CB-839 in combination with Nivolumab
Time Frame:Every 28 days from study start until disease progression or unacceptable toxicity, assessed for an expected average of 6 months
Safety Issue:
Description:Non-compartmental method of analysis will be used to analyze the plasma concentrations of CB-839.

Details

Phase:Phase 1/Phase 2
Primary Purpose:Interventional
Overall Status:Completed
Lead Sponsor:Calithera Biosciences, Inc

Trial Keywords

  • RCC
  • Melanoma (MEL)
  • NSCLC
  • Immuno-Oncology
  • Tumor Metabolism
  • Glutaminase
  • Glutaminase Inhibitor

Last Updated

August 19, 2021