A Phase 1/2 Study of the Highly Selective ROS1 Inhibitor Zidesamtinib (NVL-520) in Patients With Advanced NSCLC and Other Solid Tumors (ARROS-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 359
- 试验地点
- 63
- 主要终点
- Maximum Tolerated Dose (MTD) (Phase 1)
研究概览
简要总结
Phase 1/2, dose escalation and expansion study designed to evaluate the safety and tolerability of zidesamtinib (NVL-520), determine the recommended phase 2 dose (RP2D), and evaluate the antitumor activity in patients with advanced ROS1-positive (ROS1+) NSCLC and other advanced ROS1-positive solid tumors.
Phase 1 will determine the RP2D and, if applicable, the maximum tolerated dose (MTD) of zidesamtinib in patients with advanced ROS1-positive solid tumors.
Phase 2 will determine the objective response rate (ORR) as assessed by Blinded Independent Central Review (BICR) of zidesamtinib at the RP2D. Secondary objectives will include the duration of response (DOR), time to response (TTR), progression-free survival (PFS), overall survival (OS), and clinical benefit rate (CBR) of zidesamtinib in patients with advanced ROS1-positive NSCLC and other solid tumors.
详细描述
In Phase 2, study patients will be enrolled into 5 distinct expansion cohorts:
- Cohort 2a: ROS1-positive NSCLC naïve to Tyrosine Kinase Inhibitor (TKI) therapy and up to 1 prior chemotherapy and/or immunotherapy.
- Cohort 2b: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy.
- Cohort 2c: ROS1-positive NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy.
- Cohort 2d: ROS1-positive NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy.
- Cohort 2e: ROS1-positive solid tumor and progressed on any prior therapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 years (Cohort 2e only: Age ≥12 years).
- •Disease Criteria:
- •Phase 1: Histologically or cytologically confirmed locally advanced or metastatic solid tumor with documented ROS1 rearrangement.
- •Phase 2: Cohorts 2a, 2b, 2c and 2d: Histologically or cytologically confirmed locally advanced or metastatic NSCLC with ROS1 rearrangement.
- •Phase 2: Cohort 2e: Histologically or cytologically confirmed locally advanced or metastatic solid tumor (other than NSCLC) with ROS1 rearrangement.
- •Prior anticancer treatment (except cohort 2a).
- •Phase 1: Must have evaluable disease (target or nontarget) according to RECIST 1.
- •Phase 2: Must have measurable disease according to RECIST 1.
- •Adequate baseline organ function and bone marrow reserve.
排除标准
- •Patient's cancer has a known oncogenic driver alteration other than ROS
- •Known allergy/hypersensitivity to excipients of NVL-
- •Major surgery within 4 weeks of first dose of study drug.
- •Ongoing anticancer therapy.
- •Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study.
研究组 & 干预措施
Phase 1 dose escalation
Zidesamtinib (NVL-520) oral daily dosing
干预措施: Zidesamtinib (NVL-520) (Drug)
Cohort 2a
ROS1+ NSCLC naïve to TKI therapy and up to 1 prior chemotherapy and/or immunotherapy
干预措施: Zidesamtinib (NVL-520) (Drug)
Cohort 2b
ROS1+ NSCLC treated with 1 prior ROS1 TKI and no prior chemotherapy or immunotherapy
干预措施: Zidesamtinib (NVL-520) (Drug)
Cohort 2c
ROS1+ NSCLC treated with 1 prior ROS1 TKI and 1 prior platinum-based chemotherapy with or without immunotherapy
干预措施: Zidesamtinib (NVL-520) (Drug)
Cohort 2d
ROS1+ NSCLC treated with ≥2 prior ROS1 TKIs and up to 1 prior chemotherapy and/or immunotherapy
干预措施: Zidesamtinib (NVL-520) (Drug)
Cohort 2e
ROS1+ solid tumor and progressed on any prior therapy
干预措施: Zidesamtinib (NVL-520) (Drug)
结局指标
主要结局
Maximum Tolerated Dose (MTD) (Phase 1)
时间窗: Within 28 days of last patient dosed during dose escalation
Highest dose with dose-limiting toxicity (DLT) rate ≤ 25%
Recommended Phase 2 Dose (RP2D)
时间窗: Within 28 days of last patient dosed during dose escalation.
To determine the RP2D
Objective Response Rate (ORR) (Phase 2)
时间窗: 2-3 years after first patient dosed.
To determine ORR as assessed by BICR
次要结局
- Number of participants with treatment-emergent adverse events, as assessed by CTCAE, v5.0(Approximately 3 years.)
- Time of maximum concentration (Tmax) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Area under the curve at the end of the dosing interval (AUCtau) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Plasma concentration at the end of the dosing interval (Ctau) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Average plasma concentration (Cavg) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Area under the curve from time 0 to infinity (AUCinf) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Volume of distribution (Vz/F) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Half-life (t1/2) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Objective response rate (ORR)(2-3 years after first patient dosed)
- Maximum plasma concentration (Cmax) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Area under the curve from time 0 to 24 (AUC0-24) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Oral clearance (CL/F) of NVL-520(Pre-dose and up to 24 hours post-dose)
- Clinical benefit rate (CBR)(2-3 years after first patient dosed)
- Time to response(2-3 years after first patient dosed)
- Duration of response (DOR)(2-3 years after first patient dosed)
- Progression-free survival (PFS)(Approximately 3 years)
- Overall survival (OS)(Approximately 3 years)
- Rate of CNS progression(Approximately 3 years)
- Intracranial objective response rate (IC-ORR)(Approximately 3 years)
- Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(2-3 years after first patient dosed)
- Quality of life assessment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Lung Cancer 29 module (EORTC QLQ-LC29)(2-3 years after first patient dosed)