TIGER-2: A Phase 2, Open-label, Multicenter, Safety and Efficacy Study of Oral CO-1686 as 2nd Line EGFR-directed TKI in Patients With Mutant EGFR Non-small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 2 期
- 状态
- 终止
- 入组人数
- 318
- 试验地点
- 88
- 主要终点
- Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment
研究概览
简要总结
The purpose of this study is to evaluate the safety and anti-tumor effect of rociletinib. The trial is open-ended, which means patients will continue to take rociletinib until the study doctor determines it is no longer beneficial for them.
详细描述
This is a Phase 2, single arm, open-label, dual cohort, multicenter study evaluating the safety and efficacy of rociletinib administered orally to patients with previously treated mutant EGFR NSCLC.
Patients will be enrolled into 2 cohorts. Cohort A will enroll approximately 125 eligible patients who are centrally confirmed T790M-positive. Cohort B will be a continuation of the study and will enroll up to approximately 100 eligible patients who will be either centrally confirmed T790M-positive or T790M-negative.
All patients (for Cohort A and B) should have experienced disease progression while on treatment with the first single-agent EGFR-directed TKI (EGFR-TKI) for advanced/metastatic NSCLC. One line of chemotherapy prior to the EGFR-TKI treatment is permissible.
The study (Cohorts A and B) will consist of a screening phase to establish study eligibility and document baseline measurements, an open-label treatment phase, in which the patient will receive rociletinib to ascertain safety and efficacy until disease progression as defined by RECIST Version 1.1, clinical tumor progression, or unacceptable toxicity as assessed by the investigator. For patients with clinical progression, radiographic assessment should be performed to document evidence of radiographic progression.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Single Group
- 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
- 未提供
排除标准
- 未提供
研究组 & 干预措施
Rociletinib Mono-Therapy, T790M +ve (625mg BID)
Starting dose of 625mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.
干预措施: Rociletinib (Drug)
Rociletinib Mono-Therapy, T790M +ve (500mg BID)
Starting dose of 500mg rociletinib, taken orally twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.
干预措施: Rociletinib (Drug)
Rociletinib Mono-Therapy, T790M -ve (500mg BID)
Starting dose of 500mg rociletinib, taken twice daily, with 8 oz (240 mL) of water and with a meal or within 30 minutes after a meal. Tablets should be swallowed whole. Treatment with rociletinib is continuous and each cycle will comprise of 28 days.
干预措施: Rociletinib (Drug)
结局指标
主要结局
Objective Response Rate (ORR) According to RECIST Version 1.1 as Determined by Investigator Assessment
时间窗: Cycle 1 Day 1 to End of Treatment, up to approximately 57 months.
ORR is defined as the percentage of patients with a best overall confirmed response of partial response (PR) or complete response (CR) recorded from the start of the treatment until disease progression. For patients who continued treatment post-progression, the first date of progression was used for the analysis. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1) for target lesions, defined by and assessed as: Complete Response (CR), is disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \< 10 mm. Partial Response (PR), at least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum of longest diameter.
次要结局
- Duration of Response (DOR) in T790M Positive Patients According to RECIST Version 1.1 as Determined by Investigator Assessment(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 54 months)
- Disease Control Rate (DCR) by RECIST v1.1 as Determined by Investigator Assessment(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months)
- Progression-free Survival (PFS) in T790M Positive Patients by RECIST v1.1 as Determined by Investigator Assessment(From Cycle 1 Day 1 until disease progression or end of treatment, whichever came first, assessed up to 57 months)
- Overall Survival (OS) Determined by Investigator Assessment(Cycle 1 Day 1 to date of death, assessed up to 57 months)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in European Organization for Research and Treatment of Cancer Quality of Life Questionnaire for Patients With Cancer (EORTC QLQ-C30) Global Health Status Quality of Life Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in Dermatology Life Quality Index (DLQI)(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Alopecia Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Coughing Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dysphagia Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Dyspnoea Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Haemoptysis Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Arm or Shoulder Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Chest Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Medicine for Pain Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Pain in Other Parts Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Peripheral Neuropathy Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Change From Baseline to Cycles 5, 10 and End of Treatment (EOT) in EORTC QLQ-LC-13 Sore Mouth Scale(Baseline (Day 0), Months 5, 10 and EOT)
- Population PK (POPPK) and Exposure-Response (ER) Analysis of Rociletinib(Every 4 weeks for approximately 6 months (Day 1 of Cycles 2 to 7 inclusive))