Clinical Trials /

Study CB-839 in Combination With Nivolumab in Patients With Melanoma, ccRCC and 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:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study CB-839 in Combination With Nivolumab in Patients With ccRCC and Other Solid Tumors
  • 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 Clear Cell Renal Cell Carcinoma and Other Solid Tumors

Clinical Trial IDs

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

Conditions

  • Clear Cell Renal Cell Carcinoma
  • Melanoma
  • Non-small Cell Lung Cancer

Interventions

DrugSynonymsArms
CB-839Glutaminase inhibitorCB-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 TKI but are treatment naive to checkpoint modulators anti-PD-1/PD-L1, 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 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 have received an anti-PD-1 monotherapy in their most recent line of therapy with minimal washout (< 8 weeks), with the intent of adding CB-839 to an ongoing anti-PD-1 regimen.
  • 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 RECISTv1.1 criteria

          -  Resolution of treatment-related toxicities except alopecia

        Exclusion Criteria:

          -  Unable to receive oral medications

          -  Unable to receive oral or 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, 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

          -  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
      
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:Recruiting
Lead Sponsor:Calithera Biosciences, Inc

Trial Keywords

  • RCC
  • MEL
  • NSCLC
  • Immuno-Oncology
  • Tumor Metabolism
  • Glutaminase
  • Glutaminase Inhibitor

Last Updated

June 5, 2017