Study of CB-839 (Telaglenastat) in Combination With Talazoparib in Patients With Solid Tumors
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.
- Solid Tumor
- Clear Cell Renal Cell Carcinoma
- TNBC - Triple-Negative Breast Cancer
- Colorectal Cancer
- Eligible Ages
- Over 18 Years
- Eligible Genders
- Accepts Healthy Volunteers
-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
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.
- Phase 1/Phase 2
- Study Type
- Intervention Model
- Sequential Assignment
- Primary Purpose
- None (Open Label)
Cohort 1: CB-839 and Talazoparib
|600 mg CB-839 taken twice daily and 1 mg talazoparib taken daily||
Cohort 2: CB-839 and Talazoparib
|800 mg CB-839 taken twice daily and 1 mg talazoparib taken daily||
- Calithera Biosciences, Inc
Study ContactClinical Administrator
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.