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

Status and phase

Completed

Phase 2

Conditions

TNBC - Triple-Negative Breast Cancer

Triple Negative Breast Cancer

Treatments

Drug: Paclitaxel

Drug: CB-839

Study type

Interventional

Funder types

Industry

Identifiers

NCT03057600

CX-839-007

Details and patient eligibility

About

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.

Full 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

Enrollment

52 patients

Sex

Female

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose

Treatment

Allocation

Non-Randomized

Interventional model

Parallel Assignment

Masking

None (Open label)

52 participants in 4 patient groups

Cohort 1 - African ancestry, 3rd line+

Experimental group

Description:

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.

Treatment:

Drug: CB-839

Drug: Paclitaxel

Cohort 2 - African ancestry, 1st line

Experimental group

Description:

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.

Treatment:

Drug: CB-839

Drug: Paclitaxel

Cohort 3 - Non-African ancestry, 3rd line+

Experimental group

Description:

Intervention = Pac-CB combination 1. Participants do not self-identify as African ancestry. 2. Otherwise have the same criteria as Cohort 1.

Treatment:

Drug: CB-839

Drug: Paclitaxel

Cohort 4 - Non-African ancestry, 1st line

Experimental group