Phase 1/2 Study of BLU-451 in Advanced Cancers with EGFR exon20 Insertion Mutations
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 28
- 试验地点
- 4
- 主要终点
- 1. (Phase 1). Maximum tolerated dose (MTD) determination: Dose-limiting toxicity (DLT) rate
研究概览
简要总结
Main Objective 1 Phase 1: To determine the Maximum Tolerated Dose (MTD) and/or Recommended Phase 2 Dose (RP2D) of BLU-451 monotherapy and in combination with platinum based chemotherapy Main Objective 2 Phase 1: To characterize the safety and tolerability of BLU-451 monotherapy and in combination with platinum based chemotherapy Main Objective 1 Phase 2: To evaluate the anti-tumor activity of BLU-451 monotherapy at the RP2D using RECIST v1.1
入排标准
- 年龄范围
- 18 years 至 65+ years（65+ Years, 18-64 Years）
- 接受健康志愿者
- 是
入选标准
- •(All participants). Documented EGFR mutation, based on Next-generation sequencing (NGS) testing of tumor or liquid biopsy analyzed in a local Clinical Laboratory Improvement Amendments (CLIA) (or International Organization for Standardization (ISO) 15189)-certified or equivalent laboratory are required. Redacted copies of laboratory results must be available for Sponsor review.
- •(Only Phase 2). Must have measurable disease by RECIST 1.
- •(All participants). Able to provide a new or archived pretreatment formalin-fixed, paraffin-embedded (FFPE) tumor sample. For participants who received EGFR-targeted therapy subsequent to the most recent archived biopsy, all efforts should be made to obtain a new biopsy unless it is not safe or feasible to obtain one.
- •(All participants). Estado funcional según el Eastern Cooperative Oncology Group (ECOG) de 0 o
- •(All participants). Participants must be without seizures for at least 14 days prior to enrollment, and patients who receive treatment with anti-epileptic drugs must be on stable doses for at least 14 days prior to enrollment.
- •(All participants). Adequate hematological, renal, and hepatic function.
- •(Only Phase 1). Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per American Joint Committee on Cancer (AJCC) 8th edition) or other metastatic cancers except for primary CNS tumors (Part 1A or Part 2 only).
- •(Only Phase 1). Must have evaluable or measurable disease per RECIST v1.
- •(Only Phase 1). Progression on or after or intolerance to most recent systemic therapy.
- •(Only Phase 2). Histologically or cytologically confirmed metastatic NSCLC (stage IVA and IVB per AJCC 8th edition).
排除标准
- •Have disease that is suitable for local therapy administered with curative intent.
- •Have tumor that harbors known driver alterations (including, but not limited to ROS, BRAF V600E, ALK, RET, HER2, MET, KRAS, NTRK1/2/3, EGFR C797X, or EGFR T790M mutation). These criteria are not applicable to Phase 1 Part 1B.
- •Have NSCLC with mixed cell histology or a tumor with known histologic transformation (NSCLC to SCLC, SCLC to NSCLC, or epithelial to mesenchymal transition).
结局指标
主要结局
1. (Phase 1). Maximum tolerated dose (MTD) determination: Dose-limiting toxicity (DLT) rate
1. (Phase 1). Maximum tolerated dose (MTD) determination: Dose-limiting toxicity (DLT) rate
2. (Phase 1). Recommended Phase 2 dose (RP2D) determination: DLT, PK, PD, and preliminary safety data
2. (Phase 1). Recommended Phase 2 dose (RP2D) determination: DLT, PK, PD, and preliminary safety data
3. (Phase 1). Overall safety profile as assessed by the type, frequency, severity, timing, and relationship to study drug of adverse events (AEs), and changes in vital signs, electrocardiograms, and safety laboratory tests
3. (Phase 1). Overall safety profile as assessed by the type, frequency, severity, timing, and relationship to study drug of adverse events (AEs), and changes in vital signs, electrocardiograms, and safety laboratory tests
4. (Phase 2). Objective Response Rate (ORR)
4. (Phase 2). Objective Response Rate (ORR)
次要结局
- 1. (Phase 1). Plasma concentrations of BLU-451 as a function of time post-dosing. C3PK parameters for single (first) dose and multiple doses
- 2. (Phase 1). • ORR • DOR • Disease control rate (DCR) • Clinical benefit rate (CBR) • PFS • OS
- 3. (Phase 1). • CNS ORR • CNS DOR • CNS PFS
- 4. (Phase 1). Profile pharmacodynamic changes in gene expression levels of the EGFR pathway biomarkers dual specificity phosphatase (DUSP6) and sprouty RTK signaling antagonist 4 (SPRY4)
- 5. (Phase 2). Safety profile as assessed by the type, frequency, severity, timing, and relationship to study drug of adverse events (AEs), and changes in vital signs, electrocardiograms, and safety laboratory tests
- 6. (Phase 2). • DOR • DCR • CBR • PFS • OS
- 7. (Phase 2). • CNS ORR • CNS DOR • CNS PFS
- 8. (Phase 2). • Plasma concentrations of BLU-451 as a function of time post-dosing • PK parameters for single (first) dose and multiple doses
研究者
Medical Information
Scientific
Blueprint Medicines Corp.