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

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ClinicalTrials.gov Identifier: NCT03875313
Recruitment Status : Terminated (Slow Enrollment)
First Posted : March 14, 2019
Last Update Posted : August 18, 2021
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

Tracking Information
First Submitted Date  ICMJE March 5, 2019
First Posted Date  ICMJE March 14, 2019
Last Update Posted Date August 18, 2021
Actual Study Start Date  ICMJE May 20, 2019
Actual Primary Completion Date July 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
  • 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 ]
    Number of participants with treatment related adverse events as assessed by CTCAE v5.0
  • Maximum tolerated dose and/ or Recommended Phase 2 Dose [ Time Frame: Measured for Part 1 patients within the first 28 day cycle ]
    Incidence and nature of dose-limiting toxicities
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 13, 2019)
  • Maximum plasma concentration of CB-839 and talazoparib [ Time Frame: At the beginning of cycle 2 (each cycle is 28 days) ]
    Non-compartmental method of analysis will be used to analyze the plasma concentrations
  • Anti-tumor activity of CB-839 in combination with talazoparib [ Time Frame: Approximately every 8 weeks until disease progression, approximately 18 months ]
    Change in tumor size from baseline
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors
Official Title  ICMJE 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
Brief Summary 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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Solid Tumor
  • Clear Cell Renal Cell Carcinoma
  • TNBC - Triple-Negative Breast Cancer
  • Colorectal Cancer
  • CRC
  • RCC
  • ccRCC
Intervention  ICMJE
  • Drug: CB-839
    CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.
    Other Name: telaglenastat
  • Drug: Talazoparib
    Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.
    Other Name: Talzenna
Study Arms  ICMJE
  • Experimental: Cohort 1: CB-839 and Talazoparib
    600 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
    Interventions:
    • Drug: CB-839
    • Drug: Talazoparib
  • Experimental: Cohort 2: CB-839 and Talazoparib
    800 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
    Interventions:
    • Drug: CB-839
    • Drug: Talazoparib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Terminated
Actual Enrollment  ICMJE
 (submitted: November 23, 2020)
33
Original Estimated Enrollment  ICMJE
 (submitted: March 13, 2019)
92
Actual Study Completion Date  ICMJE July 29, 2020
Actual Primary Completion Date July 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 clear cell renal cell carcinoma (ccRCC)
  • Cohort 2: Documented incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) defined as estrogen receptor (ER), progesterone receptor (PR) negative (<1%) and human epidermal growth factor receptor 2 (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 Common Terminology Criteria for Adverse Events (CTCAE) v.5.0 from toxicities related to the prior therapy
  • Adequate renal, hepatic, and hematological function
  • Per Response Evaluation Criteria in Solid Tumours (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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03875313
Other Study ID Numbers  ICMJE CX-839-011
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Calithera Biosciences, Inc
Study Sponsor  ICMJE Calithera Biosciences, Inc
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: Sam Whiting, MD, PhD Calithera Biosciences, Inc
PRS Account Calithera Biosciences, Inc
Verification Date August 2021

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