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

Status: Active

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.

Eligibility Criteria

Inclusion 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.

Locations & Contacts

Georgia

Atlanta
Emory University Hospital / Winship Cancer Institute
Status: Active
Name Not Available

Iowa

Iowa City
University of Iowa / Holden Comprehensive Cancer Center
Status: Active
Name Not Available

New York

New York
NYP / Columbia University Medical Center / Herbert Irving Comprehensive Cancer Center
Status: Active
Name Not Available

Texas

Houston
M D Anderson Cancer Center
Status: Active
Name Not Available

Utah

Salt Lake City
Huntsman Cancer Institute / University of Utah
Status: Active
Name Not Available

Wisconsin

Madison
University of Wisconsin Hospital and Clinics
Status: Active
Name Not Available

Trial Objectives and Outline

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 Phase & Type

Trial Phase

Phase I/II

Trial Type

Treatment

Lead Organization

Lead Organization
Calithera Biosciences, Inc

Trial IDs

Primary ID CX-839-011
Secondary IDs NCI-2019-02256
Clinicaltrials.gov ID NCT03875313