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

NCT ID: NCT03875313

Last Updated: 2022-02-17

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 33 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2019-05-20
• Study Completion Date: 2020-07-29

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 poly adenosine diphosphate ribose polymerase (PARP) inhibitor talazoparib in participants with advanced/metastatic solid tumors.

Conditions

Solid Tumor; Clear Cell Renal Cell Carcinoma; TNBC - Triple-Negative Breast Cancer; Colorectal Cancer; CRC; RCC; ccRCC

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SEQUENTIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

600 mg CB-839 + 1 mg Talazoparib

600 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with advanced or metastatic solid tumors.

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Talazoparib

Intervention Type: DRUG

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

800 mg CB-839 + 1 mg Talazoparib: ccRCC

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic clear cell renal cell carcinoma (ccRCC) who received ≥ 2 prior systemic regimens including ≥ 1 vascular endothelial growth factor receptor tyrosine kinase inhibitor (VEGFR TKI) therapy.

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Talazoparib

Intervention Type: DRUG

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

800 mg CB-839 + 1 mg Talazoparib: TNBC

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with incurable/locally advanced or metastatic triple-negative breast cancer (TNBC) estrogen receptor (ER)-, progesterone receptor (PR)-, and human epidermal growth factor receptor 2 (HER2)-negative who received ≥ 1 prior line of cytotoxic chemotherapy with no prior poly adenosine diphosphate ribose polymerase (PARP) inhibitor therapy for TNBC or platinum-based chemotherapy for metastatic TNBC.

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Talazoparib

Intervention Type: DRUG

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

800 mg CB-839 + 1 mg Talazoparib: CRC

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with with incurable/locally advanced or metastatic colorectal cancer (CRC) who received appropriate oxaliplatin or irinotecan- and fluorouracil (5-FU)-based chemotherapy with or without bevacizumab.

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Talazoparib

Intervention Type: DRUG

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

800 mg CB-839 + 1 mg Talazoparib: Other Histology

800 mg CB-839 taken twice daily and 1 mg talazoparib taken once daily in participants with other tumor types (prostate, urinary bladder, pancreas, and stomach).

Group Type: EXPERIMENTAL

CB-839

Intervention Type: DRUG

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Talazoparib

Intervention Type: DRUG

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

Interventions

CB-839

CB-839 oral tablets administered twice daily with food at the assigned dose level on 28 day cycles with talazoparib.

Intervention Type: DRUG

Talazoparib

Talazoparib oral tablets administered at the standard dose once daily with or without food on 28 day cycles with CB-839.

Intervention Type: DRUG

Other Intervention Names

telaglenastat; Talzenna

Eligibility 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 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 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

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Calithera Biosciences, Inc

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Sam Whiting, MD, PhD

Role: STUDY_DIRECTOR

Calithera Biosciences, Inc

Locations

University of Alabama

Birmingham, Alabama, United States

Winship Cancer Institute of Emory University

Atlanta, Georgia, United States

University of Iowa

Iowa City, Iowa, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Columbia University

New York, New York, United States

MD Anderson

Houston, Texas, United States

South Texas Accelerated Research Therapeutics, LLC

San Antonio, Texas, United States

Huntsman Cancer Institute

Salt Lake City, Utah, United States

University of Wisconsin

Madison, Wisconsin, United States

Countries

United States

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

CX-839-011

Identifier Type: -

Identifier Source: org_study_id