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

Calithera Biosciences, Inc52 enrolled

Overview

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.

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

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Triple Negative Breast Cancer TNBC - Triple-Negative Breast Cancer

Interventions

PaclitaxelDRUG

standard weekly paclitaxel in 28-day cycles

CB-839DRUG

CB-839 administered as oral tablets twice daily (BID)

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (25)

Outcomes

Primary Outcomes

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.

Time frame: Maximum duration of follow-up for ORR was 14.8 months.

Secondary Outcomes

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.

Time frame: 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.

Data from ClinicalTrials.gov

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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.

Time frame: Maximum duration of follow-up for DOR was 14.8 months.