Study of CB-839 in Combination w/ Paclitaxel in Participants of African Ancestry and Non-African Ancestry With Advanced Triple Negative Breast Cancer (TNBC)
- Conditions
- Triple Negative Breast CancerTNBC - Triple-Negative Breast Cancer
- Interventions
- Registration Number
- NCT03057600
- Lead Sponsor
- Calithera Biosciences, Inc
- Brief Summary
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.
- 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
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- Female
- Target Recruitment
- 52
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort 2 - African ancestry, 1st line Paclitaxel Intervention = Pac-CB combination 1. Participants must self-identify as African ancestry (includes African American). 2. 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. Cohort 3 - Non-African ancestry, 3rd line+ Paclitaxel Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 1. Cohort 3 - Non-African ancestry, 3rd line+ CB-839 Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 1. Cohort 4 - Non-African ancestry, 1st line CB-839 Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 2. Cohort 2 - African ancestry, 1st line CB-839 Intervention = Pac-CB combination 1. Participants must self-identify as African ancestry (includes African American). 2. 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. Cohort 1 - African ancestry, 3rd line+ CB-839 Intervention = Paclitaxel- CB-839 (Pac-CB) combination 1. Participants must self-identify as African ancestry (includes African American). 2. 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. Cohort 1 - African ancestry, 3rd line+ Paclitaxel Intervention = Paclitaxel- CB-839 (Pac-CB) combination 1. Participants must self-identify as African ancestry (includes African American). 2. 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. Cohort 4 - Non-African ancestry, 1st line Paclitaxel Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 2.
- Primary Outcome Measures
Name Time Method Overall Response Rate (ORR) Maximum duration of follow-up for ORR was 14.8 months. 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.
- Secondary Outcome Measures
Name Time Method Overall Survival (OS) Maximum duration of follow-up for OS was 24.1 months. 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.
Duration of Response (DOR) Maximum duration of follow-up for DOR was 14.8 months. 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.Progression Free Survival (PFS) as Assessed by Investigator Maximum duration of follow-up for PFS was 17.0 months. 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.Clinical Benefit Rate (CBR) Maximum duration of follow-up for CBR was 14.8 months. 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.
Trial Locations
- Locations (25)
University of South Alabama, Mitchell Cancer Institute
🇺🇸Mobile, Alabama, United States
Winship Cancer Institute - Emory University
🇺🇸Atlanta, Georgia, United States
Baylor College of Medicine
🇺🇸Houston, Texas, United States
University of Miami
🇺🇸Miami, Florida, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
JTCC at Hackensack UMC
🇺🇸Hackensack, New Jersey, United States
University of Pennsylvania
🇺🇸Philadelphia, Pennsylvania, United States
Moffitt Cancer Center and Research Institute
🇺🇸Tampa, Florida, United States
Greenville Health System (GHS) Cancer Institute
🇺🇸Greenville, South Carolina, United States
Magee Womens Hospital - UPMC
🇺🇸Pittsburgh, Pennsylvania, United States
Saint Louis University
🇺🇸Saint Louis, Missouri, United States
University of Alabama at Brimingham
🇺🇸Birmingham, Alabama, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Northwest Medical Specialties, PLLC
🇺🇸Tacoma, Washington, United States
Northwest Georgia Oncology
🇺🇸Marietta, Georgia, United States
MD Anderson
🇺🇸Houston, Texas, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Charleston Hematology Oncology Associates
🇺🇸Charleston, South Carolina, United States
West Cancer Center
🇺🇸Germantown, Tennessee, United States
Georgetown University - Lombardi Comprehensive Cancer Center
🇺🇸Washington, District of Columbia, United States
Washington Cancer Institute
🇺🇸Washington, District of Columbia, United States
University Cancer and Blood Center
🇺🇸Athens, Georgia, United States
Weinberg Cancer Institute at Franklin Square
🇺🇸Baltimore, Maryland, United States
Froedtert and the Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States
Columbia University
🇺🇸New York, New York, United States