A Multicenter, Open Phase Ⅰ/Ⅱa Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of BR790 in Combination With Anlotinib in Subjects With Advanced Non-small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 90
- 主要终点
- Maximum tolerated dose/Recommended Phase Ⅱ Dose(MTD/RP2D)
研究概览
简要总结
This is a Phase Ⅰ/Ⅱa, multi-center, open-label study, aiming to evaluate the safety, tolerability, pharmacokinetic (PK), and efficacy of BR790 in combination with anlotinib in adult participants with advanced NSCLC.
详细描述
This study is a Phase Ⅰ/Ⅱa, multi-center, open-label study of BR790 in combination with anlotinib with a dose escalation part followed by a dose expansion part in adult subjects with advanced NSCLC. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
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 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age ≥18 and ≤75 years old.
- •Subjects with histologically or cytologically confirmed locally advanced or relapsed metastatic driver negative (EGFR, ALK, ROS, etc.) advanced NSCLC，whose disease progressed after at least 2 previous standard therapies.
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to
- •Has at least one measurable lesion per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) .
排除标准
- •Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis.
- •Has uncontrolled moderate to massive effusion.
- •Central lung squamous carcinoma along with cavum, or non-small cell lung cancer along with hemoptysis (>50ml/day).
- •Other kinds of malignancies within 5 years or for now.
- •Has not enough organ functional reserve at baseline, which met at least one of the following criteria： ANC<1.5×10^9/L, PLT<100×10^9/L, Hb<100g/L; TBIL>1.5×ULN, ALT or AST>2.5×ULN (without liver metastases) , ALT or AST>5×ULN (with liver metastases);Cr >1.5×ULN, urine protein≥++，or confirmed 24h urine protein≥1.0g;INR >1.5×ULN, PT>1.5ULN or APTT >1.5×ULN.
- •Previous use of other SHP2 inhibitors (such as TNO-155, JAB-3312, JAB-3068, RLY-1971, RMC-4630, etc.)
- •Has used anlotinib before
- •The first assessment of efficacy was PD, or occurred ≥grade 3 adverse reactions with antitumor angiogenesis small-molecule drugs (e.g. Apatinib, surufatinib, fruquintinib, etc.), or less than 6 months after the last antitumor vascular therapy.
- •Has got non remissive toxic reactions derived from previous therapies, which is over level 1 in CTC AE (5.0), alopecia and grade 2 peripheral neuropathy are not included.
研究组 & 干预措施
BR790+anlotinib
BR790 will be administered orally, variable dose on Day 1 of each 21-day cycle, Anlotinib will be administered as PO fixed dose on Day1-14 of each 21-day cycle
干预措施: BR790+anlotinib (Drug)
结局指标
主要结局
Maximum tolerated dose/Recommended Phase Ⅱ Dose(MTD/RP2D)
时间窗: 2 years
To evaluate the MTD/RP2D of BR790 in combination with anlotinib (Part 1)
Objective Response Rate (ORR)
时间窗: 2 years
To evaluate the objective response rate (ORR) of BR790 in combination with anlotinib. ORR is defined as the proportion of subjects who achieve a Complete Response (CR) or Partial Response (PR) as assessed by RECIST v1.1 (Part 2)
次要结局
- Disease Control Rate(DCR)(2 years)
- Adverse Events(AEs)(2 years)
- Plasma concentration (Cmax)(2 years)
- Overall Survival (OS)(2 years)
- Area under the plasma concentration-time curve (AUC)(2 years)
- Progression-Free Survival (PFS)(2 years)
- Duration of overall response (DOR)(2 years)