An Open-label, Non-randomized, Multi-cohort, Multi-center Phase Ia/Ib Study Evaluating the Efficacy and Safety of BBP-398 in Combination With Osimertinib in Locally Advanced or Metastatic NSCLC Patients With EGFR Mutations
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- LianBio LLC
- 入组人数
- 4
- 试验地点
- 5
- 主要终点
- Phase Ib: ORR assessed by the investigator according to RECIST v1.1
研究概览
简要总结
This is an open-label, non-randomized, multi-cohort, multi-center Phase Ia/Ib study for BBP-398 in combination with Osimertinib to evaluate the safety, tolerability, pharmacokinetics, determine MTD and/or RP2D, and anti-cancer activity in locally advanced or metastatic NSCLC patients with EGFR mutations and with previously 3rd generation EGFR-TKIs treated or EGFR-TKI-naive.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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 99 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients must have the ability to understand and the willingness to sign a written informed consent document.
- •Patients must be willing and able to comply with the scheduled visits, treatment plan, laboratory tests and other specified study procedures.
- •Age ≥18, male or female.
- •Patients are not suitable for surgical resection and must have histologically or cytologically confirmed advanced or metastatic NSCLC with documented EGFR sensitivity mutation (at any time since the initial diagnosis of NSCLC) to confirm susceptibility to EGFR-TKI therapy.
- •Patients must have measurable disease by RECIST v1.
- •ECOG performance status ≤
- •Patients must have a life expectancy of ≥12 weeks as estimated at the time of screening.
- •Patients must have adequate organ function.
排除标准
- •Patients with a known additional malignancy that is progressing or requires active treatment.
- •Patients who have previously received a SHP-2 inhibitor.
- •Patients who are hypersensitivity to BBP-398/ Osimertinib or active or inactive excipients.
- •Treatment with any of the following anti-cancer therapies prior to the first dose within the stated timeframes.
- •Pregnant or breastfeeding female patients.
- •Patients with untreated symptomatic brain metastases and/or meningeal metastases.
研究组 & 干预措施
BBP-398 + Osimertinib
Phase Ia (Dose Escalation):
Dose level 1: (starting dose level) The one lower dose level than RP2D of BBP-398 monotherapy in Chinese patients (RP2D -1) with Osimertinib 80 mg Dose level 2: RP2D The same dose level to RP2D of BBP-398 monotherapy in Chinese patients with Osimertinib 80 mg Note: The dosing interval and regimen might be changed based on emerging data of Study NAV-1001, LB1002-101 and this study. The proposed new dosing regimen will be submitted in a memo to EC for approval before execution.
Phase Ib (Efficacy Expansion):
Osimertinib 80mg QD + BBP-398 RP2D QD
干预措施: BBP-398 (Drug)
BBP-398 + Osimertinib
Phase Ia (Dose Escalation):
Dose level 1: (starting dose level) The one lower dose level than RP2D of BBP-398 monotherapy in Chinese patients (RP2D -1) with Osimertinib 80 mg Dose level 2: RP2D The same dose level to RP2D of BBP-398 monotherapy in Chinese patients with Osimertinib 80 mg Note: The dosing interval and regimen might be changed based on emerging data of Study NAV-1001, LB1002-101 and this study. The proposed new dosing regimen will be submitted in a memo to EC for approval before execution.
Phase Ib (Efficacy Expansion):
Osimertinib 80mg QD + BBP-398 RP2D QD
干预措施: osimertinib (Drug)
结局指标
主要结局
Phase Ib: ORR assessed by the investigator according to RECIST v1.1
时间窗: Every 8 weeks from first dose administration to the date of progression determined by the investigator or death due to any cause, whichever came first, assessed approximately 48 months.
ORR is defined as number of patients with confirmed responses of CR or PR, divided by the total number of treated patients with measurable disease at baseline assessed by the investigator.
Serious adverse events (SAEs)
时间窗: Administration to approximately 28 days after the last study administration
Incidence and severity of Serious adverse events (SAEs)
Treatment-emergent adverse events (TEAEs)
时间窗: From the first study administration to approximately 28 days after the last study administration
Incidence and severity of treatment-emergent adverse events (TEAEs).
次要结局
- Phase Ia: QT Interval(Approximately 6 months)
- Maximum plasma concentration (Cmax)(Approximately 6 months)
- Terminal elimination half-life (t1/2)(Approximately 6 months)
- Apparent total plasma clearance (CL/F)(Approximately 6 months)
- Accumulation ratio (Racc)(Approximately 6 months)
- Phase Ib: OS(From the first date of treatment until date of death, assessed approximately 48 months.)
- Area under the plasma concentration versus time curve (AUC)(Approximately 6 months)
- Time to Reach Maximum Plasma Concentration (Tmax)(Approximately 6 months)
- Phase Ib: PFS(Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.)
- Phase Ib: DOR(Every 8 weeks from first evaluation as CR or PR to the first evaluation as PD or death of any cause, whichever came first, assessed approximately 24 months.)