A Randomized, Open-Label, Multicenter, Phase 3 Trial Comparing Veliparib Plus Carboplatin and Paclitaxel Versus Investigator's Choice of Standard Chemotherapy in Subjects Receiving First Cytotoxic Chemotherapy for Metastatic or Advanced Non-Squamous Non-Small Cell Lung Cancer (NSCLC) and Who Are Current or Former Smokers
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 595
- 试验地点
- 140
- 主要终点
- Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
研究概览
简要总结
The purpose of this study is to evaluate the safety and efficacy of veliparib plus carboplatin and paclitaxel versus the Investigator's choice of standard chemotherapy in adults with metastatic or advanced non-squamous non-small cell lung cancer.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- All
- 接受健康志愿者
- 否
入选标准
- •Subject must be ≥ 18 years of age with life expectancy > 12 weeks.
- •Subject must have cytologically or histologically confirmed advanced or metastatic non-squamous NSCLC and are current or former smokers.
- •Subject must have NSCLC that is not amenable to surgical resection or radiation with curative intent at time of screening.
- •Subject must have at least 1 unidimensional measurable NSCLC lesion on a computed tomography (CT) scan as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
排除标准
- •Subject has a known hypersensitivity to paclitaxel or to other drugs formulated with polyethoxylated castor oil (Cremophor).
- •Subject has a known hypersensitivity to platinum compounds.
- •Subject has peripheral neuropathy ≥ grade
- •Subject has squamous NSCLC, or an untreated known epidermal growth factor receptor (EGFR) mutation of exon 19 deletion or L858R mutation in exon 21, or a known anaplastic lymphoma kinase (ALK) gene rearrangement.
- •Subject has received prior cytotoxic chemotherapy or chemoradiotherapy for NSCLC.
研究组 & 干预措施
Veliparib + Carboplatin + Paclitaxel
Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles.
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Paclitaxel (Drug)
Veliparib + Carboplatin + Paclitaxel
Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles.
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Carboplatin (Drug)
Veliparib + Carboplatin + Paclitaxel
Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles.
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Veliparib (Drug)
Veliparib + Carboplatin + Paclitaxel
Participants received 120 mg veliparib twice a day (BID) on Days -2 to 5 (7 days), carboplatin at an area under the curve (AUC) of 6 mg/mL*min on Day 1 and paclitaxel 200 mg/m² on Day 1 of each 21-day cycle for a maximum of 6 cycles.
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Pemetrexed (Drug)
Investigator's Choice Chemotherapy
Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles:
- Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m²
- Cisplatin 75 mg/m² + pemetrexed 500 mg/m²
- Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m²
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Paclitaxel (Drug)
Investigator's Choice Chemotherapy
Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles:
- Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m²
- Cisplatin 75 mg/m² + pemetrexed 500 mg/m²
- Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m²
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Carboplatin (Drug)
Investigator's Choice Chemotherapy
Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles:
- Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m²
- Cisplatin 75 mg/m² + pemetrexed 500 mg/m²
- Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m²
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Cisplatin (Drug)
Investigator's Choice Chemotherapy
Participants received Investigator's choice of standard doublet chemotherapy consisting of 1 of the following 3 options, administered on Day 1 of each 21-day cycle for a maximum of 6 cycles:
- Carboplatin AUC 6 mg/mL*min + paclitaxel 200 mg/m²
- Cisplatin 75 mg/m² + pemetrexed 500 mg/m²
- Carboplatin AUC 6 or AUC 5 mg/mL*min + pemetrexed 500 mg/m²
After completion of up to 6 cycles, optional maintenance pemetrexed was administered as 500 mg/m² on Day 1 of each 21-day cycle until toxicity required cessation of therapy, or radiographic progression occurred.
干预措施: Pemetrexed (Drug)
结局指标
主要结局
Overall Survival (OS) in the Lung Subtype Panel Positive Subgroup
时间窗: From randomization up to the data cut-off date of 15 July 2019; median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.
Overall survival is defined as the time from the date that the participant was randomized to the date of the participant's death. Overall survival was estimated using Kaplan-Meier methodology. Participants still alive at the data cut-off date were censored at the date they were last known to be alive.
次要结局
- Overall Survival in All Participants(From randomization up to the data cut-off date of 15 July 2019; the median OS follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.)
- Progression Free Survival (PFS) in the Lung Subtype Panel Positive Subgroup(From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 44.5 and 45.3 months in LSP+ participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.)
- Objective Response Rate (ORR) in the Lung Subtype Panel Positive Subgroup(Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 5.2 and 6.3 months in each group, respectively.)
- Objective Response Rate (ORR) in All Participants(Assessed on Day 1 of Cycles 3 and 5 then every 9 weeks for 1 year or until maintenance therapy was discontinued, then every 12 weeks until radiographic progression or death; median time on follow-up was 6.7 and 5.9 months in each group, respectively.)
- Progression Free Survival (PFS) in All Participants(From randomization up to the data cut-off date of 15 July 2019; the median follow-up time was 45.4 and 44.6 months in all participants for the investigator's choice chemotherapy and veliparib + C/P arms, respectively.)