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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 : Recruiting
First Posted : March 14, 2019
Last Update Posted : July 16, 2019
Sponsor:
Information provided by (Responsible Party):
Calithera Biosciences, Inc

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.

Condition or disease Intervention/treatment Phase
Solid Tumor Clear Cell Renal Cell Carcinoma TNBC - Triple-Negative Breast Cancer Colorectal Cancer CRC RCC ccRCC Drug: CB-839 Drug: Talazoparib Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 92 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : March 22, 2019
Estimated Primary Completion Date : December 2020
Estimated Study Completion Date : December 2021


Arm Intervention/treatment
Experimental: Cohort 1: CB-839 and Talazoparib
600 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
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

Experimental: Cohort 2: CB-839 and Talazoparib
800 mg CB-839 taken twice daily and 1 mg talazoparib taken daily
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




Primary Outcome Measures :
  1. 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

  2. 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


Secondary Outcome Measures :
  1. 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

  2. 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



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03875313


Contacts
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Contact: Clinical Administrator 650-870-1000 clinicaltrials@calithera.com

Locations
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United States, Georgia
Winship Cancer Institute of Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Manali Bhavi, MD    404-778-1900    manali.ajay.bhave@emory.edu   
Principal Investigator: Manali Bhave, MD         
United States, Iowa
University of Iowa Recruiting
Iowa City, Iowa, United States, 52242
Contact: Heidi Haugland    319-384-5285    heidi-haugland@uiowa.edu   
Principal Investigator: Yousef Zakharia, MD         
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Lisa Olmos    212-342-5162      
Principal Investigator: Kevin Kalinsky, MD         
United States, Texas
MD Anderson Recruiting
Houston, Texas, United States, 77030
Contact: Payal Raulji    713-745-2939    pmraulji@mdanderson.org   
Principal Investigator: Funda Meric-Bernstam, MD         
South Texas Accelerated Research Therapeutics, LLC Recruiting
San Antonio, Texas, United States, 78229
Contact: Isabel Jimenez, RN, MSN    210-593-5265    isabel.jimenez@startsa.com   
Sponsors and Collaborators
Calithera Biosciences, Inc
Investigators
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Study Director: Sam Whiting, MD, PhD Calithera Biosciences, Inc

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Responsible Party: Calithera Biosciences, Inc
ClinicalTrials.gov Identifier: NCT03875313     History of Changes
Other Study ID Numbers: CX-839-011
First Posted: March 14, 2019    Key Record Dates
Last Update Posted: July 16, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Calithera Biosciences, Inc:
Tumor Metabolism
Glutaminase Inhibitor
CB-839
telaglenastat
talazoparib
PARP Inhibitor
DNA Damage
DNA Repair
Homologous recombination deficiency
HRD
BRCA 1
BRCA 2
Additional relevant MeSH terms:
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Carcinoma, Renal Cell
Triple Negative Breast Neoplasms
Neoplasms
Neoplasms by Site
Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Kidney Diseases
Urologic Diseases
Breast Neoplasms
Breast Diseases
Skin Diseases
Talazoparib
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents