Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)

A Multicenter Phase 2 Study of the Glutaminase Inhibitor CB-839 in Combination With Paclitaxel in Patients With Advanced Triple Negative Breast Cancer (TNBC) Including Patients of African Ancestry and Non-African Ancestry

CX-839-007 is an open-label Phase 2 study of the combination of CB-839 with paclitaxel in participants of African ancestry and non-African ancestry with advanced triple negative breast cancer. Multiple single-arm cohorts will be enrolled in which 800 mg twice daily (BID) CB-839 will be administered in combination with the full approved dose of paclitaxel.

Study Overview

• Status: Completed
• Conditions: Triple Negative Breast Cancer; TNBC - Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: CB-839

Detailed Description

Participants will be enrolled into 4 cohorts, as follows:

• Cohort 1: patients of African ancestry with 2 or more lines of prior therapy for metastatic disease
• Cohort 2: patients of African ancestry with no prior lines of therapy for metastatic disease
• Cohort 3: same as cohort 1 but in patients of non-African ancestry
• Cohort 4: same as cohort 2 but in patients of non-African ancestry

• Study Type: Interventional
• Enrollment (Actual): 52
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • University of Alabama at Brimingham
    • Mobile, Alabama, United States, 36604
      • University of South Alabama, Mitchell Cancer Institute
  • Connecticut
    • New Haven, Connecticut, United States, 06511
      • Yale Cancer Center
  • District of Columbia
    • Washington, District of Columbia, United States, 20010
      • Washington Cancer Institute
    • Washington, District of Columbia, United States, 20007
      • Georgetown University - Lombardi Comprehensive Cancer Center
  • Florida
    • Miami, Florida, United States, 33176
      • University of Miami
    • Tampa, Florida, United States, 33612
      • Moffitt Cancer Center and Research Institute
  • Georgia
    • Athens, Georgia, United States, 30607
      • University Cancer and Blood Center
    • Atlanta, Georgia, United States, 30332
      • Winship Cancer Institute - Emory University
    • Marietta, Georgia, United States, 30060
      • Northwest Georgia Oncology
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Clinic Foundation
  • Maryland
    • Baltimore, Maryland, United States, 21237
      • Weinberg Cancer Institute at Franklin Square
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Hospital
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Saint Louis University
  • New Jersey
    • Hackensack, New Jersey, United States, 07601
      • JTCC at Hackensack UMC
  • New York
    • New York, New York, United States, 10032
      • Columbia University
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15213
      • Magee Womens Hospital - UPMC
  • South Carolina
    • Charleston, South Carolina, United States, 29414
      • Charleston Hematology Oncology Associates
    • Greenville, South Carolina, United States, 29605
      • Greenville Health System (GHS) Cancer Institute
  • Tennessee
    • Germantown, Tennessee, United States, 38138
      • West Cancer Center
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine
    • Houston, Texas, United States, 77030
      • MD Anderson
  • Washington
    • Tacoma, Washington, United States, 98405
      • Northwest Medical Specialties, PLLC
  • Wisconsin
    • Milwaukee, Wisconsin, United States, 53226
      • Froedtert and The Medical College of Wisconsin

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 14 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Key Inclusion Criteria:

• Meets criteria for 1 of the 4 defined study cohorts
• TNBC, defined as estrogen receptor (ER) and progesterone receptor (PR) negative (< 1% by immunohistochemistry) and human epidermal growth factor receptor 2 (HER2)-negative (immunohistochemistry 0 to 1+ or fluorescence in situ hybridization [FISH] negative)
• Metastatic disease or locally-advanced disease not amenable to curative intent treatment
• Adequate hepatic, renal, cardiac, and hematologic function
• Eastern Cooperative Oncology Group (ECOG) performance status 0-1
• Recovery to baseline or ≤ Grade 1 Common Terminology Criteria for Adverse Events (CTCAE) version.4.0

Key Exclusion Criteria:

• Known brain metastases or central nervous system (CNS) cancer unless adequately treated with radiotherapy and/or surgery and stable for ≥ 2 mo
• Unable to receive oral medications
• Known hypersensitivity to Cremophor®-based agents
• Major surgery within 28 days of Cycle 1 Day 1

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1 - African ancestry, 3rd line+; Intervention = Paclitaxel- CB-839 (Pac-CB) combination; Participants must self-identify as African ancestry (includes African American).; At least 2 prior lines of systemic therapy for advanced/metastatic disease including a taxane.Prior taxane (paclitaxel, docetaxel, or nab-paclitaxel) for advanced/metastatic disease is required but must not have been received in the immediate prior line of therapy.Systemic neoadjuvant and/or adjuvant therapy is considered a line of therapy for advanced/metastatic disease if the time to recurrence from completion of treatment was ≤ 12 mo.	Drug: Paclitaxel; standard weekly paclitaxel in 28-day cycles; Other Names: Taxane; Drug: CB-839; CB-839 administered as oral tablets twice daily (BID); Other Names: telaglenastat
Experimental: Cohort 2 - African ancestry, 1st line; Intervention = Pac-CB combination; Participants must self-identify as African ancestry (includes African American).; No prior systemic therapy for advanced or metastatic disease.Systemic neoadjuvant or adjuvant therapy, including taxane, is allowed if time to recurrence was > 12 mo.	Drug: Paclitaxel; standard weekly paclitaxel in 28-day cycles; Other Names: Taxane; Drug: CB-839; CB-839 administered as oral tablets twice daily (BID); Other Names: telaglenastat
Experimental: Cohort 3 - Non-African ancestry, 3rd line+; Intervention = Pac-CB combination; Participants do not self-identify as African ancestry.; Otherwise have the same criteria as Cohort 1.	Drug: Paclitaxel; standard weekly paclitaxel in 28-day cycles; Other Names: Taxane; Drug: CB-839; CB-839 administered as oral tablets twice daily (BID); Other Names: telaglenastat
Experimental: Cohort 4 - Non-African ancestry, 1st line; Intervention = Pac-CB combination; Participants do not self-identify as African ancestry.; Otherwise have the same criteria as Cohort 2.	Drug: Paclitaxel; standard weekly paclitaxel in 28-day cycles; Other Names: Taxane; Drug: CB-839; CB-839 administered as oral tablets twice daily (BID); Other Names: telaglenastat

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Response Rate (ORR)	ORR is defined as the percentage of patients with complete response (CR) or partial response (PR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessment performed no less than 4 weeks after the criteria for response were first met.	Maximum duration of follow-up for ORR was 14.8 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Progression Free Survival (PFS) as Assessed by Investigator	PFS was defined as time from the first dose date to the earlier of either progression of disease per RECIST v1.1 or death from any cause. The duration of progression-free survival was censored at the date of last radiographic disease if the patient was alive and progression free at the time of analysis data cutoff, disease progression or death occurred after missing data for 2 consecutive radiographic disease assessments, or patient received non-protocol TNBC treatment prior to documentation of disease progression. Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% confidence interval (CI) is used. Progressive Disease (PD) per RECIST 1.1: At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.	Maximum duration of follow-up for PFS was 17.0 months.
Overall Survival (OS)	Overall survival is defined as the time from the first dose date to death due to any cause. For patients alive at time of analysis, overall survival will be censored at the time when the patient is last known to be alive.Kaplan-Meier product-limit estimates. Brookmeyer-Crowley methodology for a non-parametric 95% CI is used. Median is defined to be the smallest observed survival time for which the value of the estimated survival function is less than or equal to 0.5.	Maximum duration of follow-up for OS was 24.1 months.
Duration of Response (DOR)	Duration of response is defined as the time between the first documentation of a confirmed PR or a CR to the first documentation of PD or death, whichever occurs first. The duration of response will be censored at the date of last radiographic disease if the patient is alive and progression free at the time of database lock, disease progression or death occurs after missing data for two consecutive radiographic disease assessments, or patient receives non-protocol TNBC treatment prior to documentation of disease progression. RECIST v1.1 criteria: Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study. In addition, the sum must also demonstrate an absolute increase of at least 5 mm.	Maximum duration of follow-up for DOR was 14.8 months.
Clinical Benefit Rate (CBR)	Clinical Benefit Rate is defined as the percentage of patients with best response of CR, PR, or SD per RECIST v1.1 criteria lasting ≥ 16 weeks for 3rd line + patients and ≥ 24 weeks for 1st line patients. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.	Maximum duration of follow-up for CBR was 14.8 months.

Collaborators and Investigators

• Sponsor: Calithera Biosciences, Inc
• Investigators: Study Director: Sam Whiting, MD, PhD, Calithera Biosciences, Inc

Publications and helpful links

Helpful Links

• Company Website

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2017
• Primary Completion (Actual): November 25, 2019
• Study Completion (Actual): November 25, 2019

Study Registration Dates

• First Submitted: February 10, 2017
• First Submitted That Met QC Criteria: February 17, 2017
• First Posted (Actual): February 20, 2017

Study Record Updates

• Last Update Posted (Actual): September 28, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Keywords: African American; TNBC; Glutamine; Tumor Metabolism; Glutaminase Inhibitor; CB-839; Glutaminase; African ancestry
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Triple Negative Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel
• Other Study ID Numbers: CX-839-007

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No