Clinical Trials /

Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors

NCT03875313

Description:

This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor CB-839 with the PARP inhibitor talazoparib in participants with advanced/metastatic solid tumors.

Related Conditions:
  • Breast Carcinoma
  • Malignant Solid Tumor
Recruiting Status:

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors
  • Official Title: A Phase 1b/2 Open Label, Dose Escalation and Expansion Study of the Glutaminase Inhibitor CB-839 in Combination With the PARP Inhibitor Talazoparib in Patients With Advanced or Metastatic Solid Tumors

Clinical Trial IDs

  • ORG STUDY ID: CX-839-011
  • NCT ID: NCT03875313

Conditions

  • Solid Tumor
  • Clear Cell Renal Cell Carcinoma
  • TNBC - Triple-Negative Breast Cancer
  • Colorectal Cancer
  • CRC
  • RCC
  • ccRCC

Interventions

DrugSynonymsArms
CB-839telaglenastatCohort 1: CB-839 and Talazoparib
TalazoparibTalzennaCohort 1: CB-839 and Talazoparib

Purpose

This is a Phase 1b/2 study to determine the recommended phase 2 dose (RP2D), safety and tolerability, pharmacokinetics (PK) and clinical activity of the glutaminase inhibitor CB-839 with the PARP inhibitor talazoparib in participants with advanced/metastatic solid tumors.

Detailed Description

      This is a multicenter, open-label, dose-escalation and dose-expansion study. In Part 1,
      escalating doses of CB-839 will be paired with the standard dose of talazoparib in order to
      determine the maximum tolerated dose (MTD) and/or the RP2D of the regimen and to characterize
      the safety and tolerability profile of the combination in participants with
      advanced/metastatic solid tumors.

      In Part 2, the combination of CB-839 and talazoparib will be evaluated at the RP2D determined
      in Part 1 to evaluate the anti-cancer activity of the regimen in participants with
      advanced/metastatic clear cell RCC, TNBC or CRC.
    

Trial Arms

NameTypeDescriptionInterventions
Cohort 1: CB-839 and TalazoparibExperimental600 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
  • CB-839
  • Talazoparib
Cohort 2: CB-839 and TalazoparibExperimental800 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
  • CB-839
  • Talazoparib

Eligibility Criteria

        Inclusion Criteria:

        (Part 1)

        -Documented incurable/locally advanced or metastatic solid tumors that have either relapsed
        or are refractory or intolerant to standard therapies of proven clinical benefit.

        (Part 2) Meets 1 of the 3 defined cohorts:

          -  Cohort 1: Documented incurable/locally advanced or metastatic ccRCC

          -  Cohort 2: Documented incurable/locally advanced or metastatic TNBC defined as ER, PR
             negative (<1%) and HER2 negative (immunohistochemistry 0 to 1+ or fluorescence in situ
             hybridization [FISH] negative)

          -  Cohort 3: incurable/locally advanced or metastatic CRC

        For both Parts 1 & 2:

          -  Recovery to baseline or ≤ Grade 1 CTCAE v.5.0 from toxicities related to the prior
             therapy

          -  Adequate renal, hepatic, and hematological function

          -  Per RECIST v1.1 evaluable disease (Part 1) or measurable disease (Part 2)

          -  Ability to provide written consent in accordance with federal, local and institutional
             guidelines

          -  Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1

        Exclusion Criteria for both Parts 1 & 2:

          -  Prior treatment with CB-839 or a PARP inhibitor

          -  Unable to received oral medications

          -  Active and/or untreated central nervous system metastasis. Patients with treated brain
             metastases must have (1) documented radiographic stability of at least 4 weeks
             duration demonstrated on baseline central nervous system (CNS) imaging prior to study
             treatment and (2) be symptomatically stable and off steroids for at least 2 weeks
             before administration of any study treatment.

          -  Major surgery within 28 days prior to first dose of study drug

          -  Receipt of any anticancer therapy within the following windows: small molecule
             tyrosine kinase inhibitor therapy (including investigational) within the prior 2 weeks
             or 5 half-lives prior to C1D1, whichever is longer; any type of anti-cancer antibody
             or cytotoxic chemotherapy within 4 weeks prior to C1D1; radiation therapy for bone
             metastasis within 2 weeks prior or any other external radiation therapy within 4 weeks
             prior to C1D1; patients with clinically relevant ongoing complications from prior
             radiation therapy are not eligible.
      
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 in combination with talazoparib: Number of participants with treatment related adverse events
Time Frame:Start of treatment to 28 days post treatment
Safety Issue:
Description:Number of participants with treatment related adverse events as assessed by CTCAE v5.0

Secondary Outcome Measures

Measure:Maximum plasma concentration of CB-839 and talazoparib
Time Frame:At the beginning of cycle 2 (each cycle is 28 days)
Safety Issue:
Description:Non-compartmental method of analysis will be used to analyze the plasma concentrations
Measure:Anti-tumor activity of CB-839 in combination with talazoparib
Time Frame:Approximately every 8 weeks until disease progression, approximately 18 months
Safety Issue:
Description:Change in tumor size from baseline

Details

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

Trial Keywords

  • Tumor Metabolism
  • Glutaminase Inhibitor
  • CB-839
  • telaglenastat
  • talazoparib
  • PARP Inhibitor
  • DNA Damage
  • DNA Repair
  • Homologous recombination deficiency
  • HRD
  • BRCA 1
  • BRCA 2

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