NCT05256290进行中（未招募）1 期
A Phase 1/2 Study to Assess BDTX-1535, an Oral EGFR Inhibitor, in Patients With Glioblastoma or Non-Small Cell Lung Cancer
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 200
- 试验地点
- 50
- 主要终点
- Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of silevertinib (BDTX-1535)
研究概览
简要总结
BDTX-1535-101 is an open-label, Phase 1 dose escalation and Phase 2 multiple cohort study designed to evaluate the safety, pharmacokinetics (PK), optimal dosage, central nervous system (CNS) activity, and antitumor activity of silevertinib (BDTX-1535). The study population comprises adults with either advanced/metastatic non-small cell lung cancer (NSCLC) with non-classical or acquired epidermal growth factor receptor (EGFR) resistance (EGFR C797S) mutations with or without CNS disease (in Phase 1 and Phase 2), or glioblastoma (GBM) expressing EGFR alterations (Phase 1 only). All patients will self-administer silevertinib (BDTX-1535) monotherapy by mouth in 21-day cycles.
Phase 1 enrollment is now complete. Phase 2 is currently ongoing.
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
- •Phase 2 Eligibility:
- •Key Inclusion Criteria Required for locally advanced or metastatic NSCLC:
- •Measurable disease by RECIST 1.1 criteria.
- •Adequate bone marrow or organ function.
- •Life expectancy of ≥ 3 months.
- •Sufficient performance status.
- •Confirmed NSCLC, without small cell lung cancer transformation with or without brain metastases.
- •Disease progression following or intolerance of standard of care (excluding patients in the treatment-naïve non-classical driver cohort):
- •Cohort 1 (Non-Classical driver cohort): Advanced/metastatic NSCLC with a non-classical driver EGFR mutation (eg, G719X) following up to 2 lines of therapy with only 1 prior EGFR TKI regimen (third-generation preferred; other approved EGFR TKI acceptable).
- •Cohort 2 (Acquired resistance C797S cohort): Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only one EGFR TKI, which must be a third generation EGFR TKI (eg, osimertinib).
- •Cohort 3 (First-line non-classical driver cohort): Treatment-naïve advanced/metastatic NSCLC with a non-classical driver EGFR mutation (1 cycle of chemotherapy or immune checkpoint inhibitor are permitted). Patients with co-occurring L858R mutations and a non-classical mutation are eligible for inclusion.
- •Identification of one (or more) of the following EGFR mutations by Next Generation Sequencing (NGS) as determined by a local assay performed in a validated laboratory in the absence of other known resistance mutations (eg, T790M, MET):
- •Non-classical driver EGFR mutations (eg, L861R, S768I, G719X).
- •EGFR acquired resistance mutation (eg, C797S) to a 3rd generation EGFR TKI.
- •For Phase 2, dose expansion, patients in Cohort 1 who received 3rd generation EGFR TKI (eg, osimertinib), the NGS report within 6 months prior to the start of Screening is acceptable. For patients in Cohort 2, the NGS report must be from the last disease progression on the immediate prior therapy. For patients in Cohort 3, the NGS report must be at the time of diagnosis.
排除标准
- •Known resistant mutations in tumor tissue or by liquid biopsy (eg, T790M, MET).
- •Received more than 1 EGFR TKI therapy (ie, erlotinib or gefitinib) for the treatment of metastatic or recurrent EGFR NSCLC.
- •Any history of interstitial lung disease related to EGFR TKI use.
- •Symptomatic or radiographic leptomeningeal disease.
- •Symptomatic brain metastases or spinal cord compression requiring urgent clinical intervention.
- •Unresolved toxicity from prior therapy.
- •Significant cardiovascular disease.
- •Major surgery within 4 weeks of study entry or planned during study.
- •Ongoing or recent anticancer therapy or radiation therapy.
- •Evidence of malignancy (other than study-specific malignancies) requiring active therapy within the next 2 years.
- •Active hepatitis B or C infection and/or known human immunodeficiency virus (HIV) carrier.
- •Poorly controlled gastrointestinal disorders.
研究组 & 干预措施
Phase 1 Dose Escalation - Monotherapy (Recruitment Closed)
Experimental
- Advanced/metastatic NSCLC with acquired resistance EGFR mutation (eg, C797S), following a 3rd generation EGFR inhibitor in the 1st line setting (in the absence of concurrent T790M).
- Advanced/metastatic NSCLC with non-classical EGFR mutation (eg, G719X) following standard-of-care therapy with an EGFR inhibitor
- Recurrent GBM with confirmed EGFR alterations (including amplification, mutation, and/or variant)
干预措施: silevertinib (BDTX-1535) monotherapy (Drug)
Phase 2 Cohort 1: NSCLC EGFR Non-Classical Driver Mutations
Experimental
Advanced/metastatic NSCLC with a non-classical driver EGFR mutation following up to 2 lines of therapy with only 1 prior EGFR targeted regimen (third-generation preferred; other approved EGFR inhibitors acceptable)
干预措施: silevertinib (BDTX-1535) monotherapy (Drug)
Phase 2 Cohort 2: NSCLC EGFR Acquired Resistance (C797S) Mutation
Experimental
Advanced/metastatic NSCLC with the acquired resistance C797S EGFR mutation following up to 2 lines of therapy, including only 1 EGFR targeted regimen, which must be a third generation EGFR TKI (eg, osimertinib)
干预措施: silevertinib (BDTX-1535) monotherapy (Drug)
结局指标
主要结局
Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of silevertinib (BDTX-1535)
时间窗: The first treatment 21-day cycle (Cycle 1)
Dose-limiting toxicities (DLTs) in Cycle 1
Phase 2: To assess antitumor efficacy of silevertinib (BDTX-1535)
时间窗: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1
Phase 2: To assess antitumor efficacy of silevertinib (BDTX-1535)
时间窗: Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days)
Objective response rate (ORR) as assessed by Investigator using RECIST version 1.1
Phase 1 Dose Escalation: To determine the maximum tolerated dose (MTD), if one exists, and the preliminary recommended Phase 2 dose(s) (RP2D[s]) of silevertinib (BDTX-1535)
时间窗: The first treatment 21-day cycle (Cycle 1)
Dose-limiting toxicities (DLTs) in Cycle 1
次要结局
- Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)(Through study completion, approximately 1 year)
- Phase 1 and Phase 2: To characterize the plasma concentration of silevertinib (BDTX-1535) following single and multiple dosing(Cycle 1 Days 1, 2, 15, and 16, Cycles 2 to 5 Day 1, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 21 days))
- Phase 1: To assess the preliminary antitumor activity of silevertinib (BDTX-1535) by objective response as assessed by RECIST version 1.1 (for patients with NSCLC) or Response Assessment in Neuro-oncology (RANO) (for patients with GBM)(Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 1: To assess the effect of tablet formulation on the plasma concentration of silevertinib (BDTX-1535)(Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days))
- Phase 1: To assess the effect of food on the plasma concentration of silevertinib (BDTX-1535)(Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days))
- Phase 2: To assess duration of tumor response by RECIST version 1.1(Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 2: To assess progression free survival by RECIST version 1.1(Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 2: To determine the optimal dosage of silevertinib (BDTX-1535) (100 mg or 200 mg daily dose)(At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2)
- Phase 1 and Phase 2: Incidence and severity of treatment-emergent adverse events (TEAEs)(Through study completion, approximately 1 year)
- Phase 1 and Phase 2: To characterize the plasma concentration of silevertinib (BDTX-1535) following single and multiple dosing(Cycle 1 Days 1, 2, 15, and 16, Cycles 2 to 5 Day 1, and Day 1 of every other cycle thereafter to study completion, approximately 1 year (each cycle is 21 days))
- Phase 1: To assess the preliminary antitumor activity of silevertinib (BDTX-1535) by objective response as assessed by RECIST version 1.1 (for patients with NSCLC) or Response Assessment in Neuro-oncology (RANO) (for patients with GBM)(Day 1 every 2 cycles starting on Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 1: To assess the effect of tablet formulation on the plasma concentration of silevertinib (BDTX-1535)(Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days))
- Phase 1: To assess the effect of food on the plasma concentration of silevertinib (BDTX-1535)(Two timepoints during the first cycle: Cycle 0 (7 days prior to Cycle 1 Day 1) and Cycle 1 Day 1 only (each cycle is 21 days))
- Phase 2: To assess duration of tumor response by RECIST version 1.1(Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 2: To assess progression free survival by RECIST version 1.1(Day 1 every 2 cycles starting at Cycle 3 Day 1 to study completion, approximately 1 year (each cycle is 21 days))
- Phase 2: To determine the optimal dosage of silevertinib (BDTX-1535) (100 mg or 200 mg daily dose)(At least the first treatment 21-day cycle (Cycle 1) for select patients enrolled into the Phase 2)
研究者
研究点 (50)
Loading locations...
相似试验
终止
1 期
A Study of BDTX-189, an Orally Available Allosteric ErbB Inhibitor, in Patients With Advanced Solid Tumors.Solid TumorNCT04209465Black Diamond Therapeutics, Inc.91
已完成
1 期
A Study of the Safety, Tolerability, and Effects of Cobimetinib and GDC-0994 in Patients With Locally Advanced or Metastatic Solid TumorsNon-Small Cell Lung Cancer, Metastatic Colorectal Cancer, Metastatic Non Small Cell Lung Cancer, Metastatic Cancers, MelanomaNCT02457793Genentech, Inc.24
已完成
2 期
A Study With BIBF 1120 in Patients With Hormone Refractory Prostate CancerProstatic NeoplasmsNCT02182063Boehringer Ingelheim81
已完成
2 期
Efficacy and Safety of BGB-290 in the Treatment of Metastatic HER2-Negative Breast Cancer Patients With BRCA Mutation in ChinaHER2-negative Breast CancerNCT03575065BeiGene88
已完成
2 期
Efficacy and Safety Study of BDB-001 Injection in Patients With Moderate to Severe Hidradenitis Suppurativa (HS)Hidradenitis SuppurativaNCT05093855Staidson (Beijing) Biopharmaceuticals Co., Ltd41
相关资讯
Black Diamond Therapeutics Reports Promising Phase 2 Data for Silevertinib in EGFR-Mutant Cancers- Black Diamond Therapeutics reported 60% objective response rate and 86% CNS response rate for silevertinib in frontline non-classical EGFR-mutant NSCLC patients.
- The company plans to initiate a randomized Phase 2 trial for silevertinib in newly diagnosed EGFR-altered glioblastoma in Q2 2026.
- Updated clinical data including preliminary duration of response and progression-free survival data will be presented at a medical meeting in Q2 2026.
- The company ended 2025 with $128.7 million in cash, sufficient to fund operations into the second half of 2028.6 months agoBDTX-1535 Shows Promise in Relapsed/Refractory EGFR-Mutant NSCLC• BDTX-1535, a fourth-generation EGFR TKI, demonstrates encouraging clinical activity in relapsed/refractory EGFR-mutant non-small cell lung cancer (NSCLC).
• A phase 2 trial showed a 42% objective response rate (ORR) in patients with osimertinib-resistant EGFR mutations, including C797S.
• The 200 mg daily dose of BDTX-1535 was well-tolerated, with mostly mild to moderate adverse events and no new safety signals observed.
• Black Diamond Therapeutics anticipates sharing initial results from the first-line cohort in Q1 2025 and discussing potential registration paths.last year