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
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 入组人数
- 52
- 试验地点
- 25
- 主要终点
- Overall Response Rate (ORR)
研究概览
简要总结
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.
详细描述
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: CB-839 (Drug)
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.
干预措施: Paclitaxel (Drug)
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.
干预措施: CB-839 (Drug)
结局指标
主要结局
Overall Response Rate (ORR)
时间窗: 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.
次要结局
- Overall Survival (OS)(Maximum duration of follow-up for OS was 24.1 months.)
- Duration of Response (DOR)(Maximum duration of follow-up for DOR was 14.8 months.)
- Progression Free Survival (PFS) as Assessed by Investigator(Maximum duration of follow-up for PFS was 17.0 months.)
- Clinical Benefit Rate (CBR)(Maximum duration of follow-up for CBR was 14.8 months.)