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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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.

Study Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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 names:
    • 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 names:
    • 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 names:
    • 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 names:
    • Talzenna

Recruiting Locations

University of Alabama
Birmingham, Alabama 35294
Contact:
Likesar (Keisha) McCray
205-975-7265
lmccray@uab.edu

More Details

NCT ID
NCT03875313
Status
Recruiting
Sponsor
Calithera Biosciences, Inc

Study Contact

Clinical Administrator
650-870-1000
clinicaltrials@calithera.com

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.