A Phase 1a/1b Study of the Selective Tyrosine Kinase Inhibitor NVL-330 in Patients With Advanced or Metastatic HER2-altered NSCLC (HEROEX-1)
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 200
- 试验地点
- 40
- 主要终点
- Recommended Phase 2 Dose (RP2D)
研究概览
简要总结
Phase 1a/1b dose escalation and expansion study designed to evaluate the safety and tolerability of NVL-330, determine the recommended Phase 2 dose (RP2D), and evaluate the antitumor activity in participants with advanced or metastatic human epidermal growth factor receptor 2 (HER2) -altered non-small lung cancer (NSCLC).
Phase 1a dose escalation is designed to assess the safety and tolerability of NVL-330 and to select the candidate RP2D(s) and, if applicable, the MTD.
Phase 1b expansion is designed to further evaluate the overall safety and tolerability of the candidate RP2D(s) of NVL-330 and to determine the RP2D of NVL-330 in participants with advanced or metastatic HER2 mutant NSCLC.
详细描述
The planned Phase 1a/1b first-in-human study is designed as a two-part clinical trial to investigate NVL-330 in pre-treated participants with advanced or metastatic HER2-altered NSCLC. The dose escalation phase of the trial is designed to enroll a set number of participants per cohort at protocol defined dose levels.
After the initial participants are treated at a given dose level and monitored for at least 28 days, available data will be reviewed, and initiation of the next dosing group will proceed with consideration given to the overall safety profile.
The expansion phase of the trial is designed to further evaluate safety and activity and to confirm the RP2D(s).
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
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥ 18 years
- •Histologically or cytologically confirmed locally advanced or metastatic NSCLC
- •Documented HER2 status as follows:
- •Phase 1a: Documented oncogenic HER2 mutation such as HER2 exon20 insertion mutations or single nucleotide variants or HER2 amplification.
- •Phase 1b: Documented oncogenic HER2 mutation.
- •Identification of lesions as follows:
- •Phase 1a: Must have evaluable disease (target or nontarget) according to RECIST 1.
- •Phase 1b: Must have measurable disease, defined as ≥ 1 radiologically measurable target lesion according to RECIST 1.
- •Adequate organ function and bone marrow reserve
排除标准
- •Participant's cancer has known oncogenic driver alteration other than HER2
- •Known allergy/hypersensitivity to excipients of NVL-330
- •Major surgery within 4 weeks of the first dose of study drug
- •Ongoing or recent anticancer therapy
- •Actively receiving systemic treatment or direct medical intervention on another therapeutic clinical study
研究组 & 干预措施
Phase 1a dose escalation
NVL-330 oral daily dosing
干预措施: NVL-330 (Drug)
Phase 1b dose expansion
NVL-330 oral daily dosing
干预措施: NVL-330 (Drug)
结局指标
主要结局
Recommended Phase 2 Dose (RP2D)
时间窗: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
To determine up to 2 RP2D Candidates
Maximum Tolerated Dose (MTD)
时间窗: As determined by incidence of DLTs during the first 28 days of treatment (ie, Cycle 1)
If applicable, to determine the MTD
Incidence and severity of Treatment Emergent Adverse Events (TEAEs)
时间窗: First dose of study drug through 30 days after the last dose of study drug
Number of participants with TEAEs as assessed by CTCAE, v5.0
次要结局
- Effect of Food on Maximum Plasma Concentration (Cmax) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Time to Response (TTR)(Approximately 3 years)
- Effect of Food on Area Under the Curve from Time 0 to 24 (AUC0-24) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Effect of Food on Time of Maximum Concentration (Tmax) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Time of maximum concentration (Tmax) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve at the End of the Dosing Interval (AUCtau) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve at the End of the Dosing Interval (AUCtau - dose normalized) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Effect of Food on Area Under the Curve from Time 0 to Infinity (AUCinf) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Plasma concentration 24 hours post-dose (C24) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Maximum plasma concentration (Cmax) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Maximum plasma concentration (Cmax- dose normalized) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Plasma concentration at the end of the dosing interval (Ctau) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Average plasma concentration (Cavg) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve From Time 0 to Infinity (AUCinf) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Oral clearance (CL/F) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Volume of Distribution (Vz/F) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Accumulation Ratio of NVL-330(Pre-dose and up to 24 hours post-dose)
- Half-life (t1/2) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve From Time 0 to 24 (AUC0-24) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve From Time 0 to 24 (AUC0-24 - dose normalized) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Area Under the Curve From Time 0 to Infinity (AUCinf - dose normalized) of NVL-330(Pre-dose and up to 24 hours post-dose)
- Objective Response Rate (ORR)(2 -3 years after first participant dosed)
- Duration of Response (DOR)(2 to 3 years after first participant dosed)
- Intracranial Objective Response Rate (IC-ORR)(2 to 3 years after first participant dosed)
- Intracranial Duration of Response (IC-DOR)(2 to 3 years after first participant dosed)