EUCTR2020-005492-12-DK进行中（未招募）1 期
MasterKey-01: A Phase 1/2, Open-label, Two-part, Multicenter Study to Assess the Safety, Tolerability, Pharmacokinetics, and Antitumor Activity of BDTX-189, an Inhibitor of Allosteric ErbB Mutations, in Patients with Advanced Solid Malignancies - MasterKey-01
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 619
研究概览
简要总结
暂无简介。
研究设计
- 研究类型
- Interventional clinical trial of medicinal product
入排标准
- 性别
- All
入选标准
- •Part A and Part B:
- •Histologically- or cytologically-confirmed locally advanced or metastatic solid tumor with documented recurrence or disease progression from standard anticancer therapy in the advanced/metastatic setting
- •Part A Dose Escalation Only:
- •No standard therapy available according to the Investigator
- •Patients with solid tumor with alterations that may be associated with antitumor activity based on preclinical data for BDTX-189 such as:
- •- Allosteric HER2 or HER3 mutation(s)
- •- EGFR or HER2 exon 20 insertion mutation
- •- HER2 amplified or overexpressing tumor
- •- EGFR exon 19 deletion or L858R mutation
- •Mutations must have been determined by a validated next-generation sequencing (NGS) test routinely used by each institution using tissue and/or plasma and performed in a Clinical Laboratory Improvement Amendments (CLIA)-certified or equivalent laboratory. A list of eligible validated oncogenic mutations from 1 of the 7 MTCs is provided in Appendix I.
- •Part A Safety Expansion Only:
- •No standard therapy available according to the Investigator
- •Patients with one of the following mutations and tumor pairs:
- •- Allosteric HER2 mutation in patients with NSCLC, breast cancer, biliary tract cancer, or cervical cancer
- •- EGFR or HER2 exon 20 insertion mutation in patients with NSCLC
- •- HER2 amplified or overexpressing tumor from the following cancer types: breast, gastric, gastroesophageal, colorectal, endometrial, biliary tract, cancer of unknown primary (CUP), and NSCLC
- •Mutations must have been determined by a validated NGS test routinely used by each institution using tissue and/or plasma and performed in a CLIA-certified or equivalent laboratory. A list of eligible validated oncogenic mutations from 1 of the 7 MTCs are provided in Appendix I.
- •Note: The Sponsor reserves the right to prioritize tumor/genomic alteration pairs and o cap enrollment for any of these based on the Sponsor’s portfolio decision-making process.
- •Mandatory archival tumor tissue or willing to undergo pretreatment biopsy if no archival tissue available (Section 5.7.1).
- •Measurable disease according to RECIST version 1.1 (Appendix B).
- •Part B Only:
- •Patients with locally advanced or metastatic:
- •- NSCLC who have received at least one prior platinum-containing regimen (with or without an anti-programmed death-ligand 1 [PD-(L)1] antibody) and no more 2 prior regimens for advanced NSCLC. Patients with no prior therapy who refuse standard therapy may also be eligible following discussion and approval by the Sponsor’s Medical Monitor.
- •- Solid tumor other than NSCLC who have received at least one and no more than 3 prior regimens for advanced cancer.
- •Patients with solid tumor(s) harboring an:
- •- Allosteric HER2 mutation
- •- EGFR exon 20 insertion mutation or HER2 exon 20 insertion or point mutation
- •Mutations must have been determined by a validated NGS test routinely used by each institution using tissue and/or plasma and performed in a CLIA-certified or equivalent laboratory. A list of eligible validated oncogenic mutations from 1 of the 7 MTCs is provided in Appendix I.
- •Eligible patients will be assigned to one of the 5 following cohorts:
- •Cohort 1: NSCLC with an allosteric EGFR exon 20 insertion mutation from MTC-A
- •Cohort 2: NSCLC with an allosteric HER2 exon 20 insertion mutation from MTC-B or point mutation from MTC-C
- •Cohort 3: Breast cancer with an allosteric HER2 mutation from MTC-B, MTC-C, MTC-D, MTC-E, or MTC-F
- •Cohort 4: NSCLC, biliary tract cancer, or cervical c
排除标准
- •Part A and Part B:
- •Clinical laboratory values meeting the following criteria within 4 weeks (28 days) prior to baseline:
- •- Serum creatinine =1.5 × upper limit of normal (ULN) AND calculated creatinine clearance =60 mL/min using Cockcroft-Gault equation.
- •- Total bilirubin =1.5 × ULN or =3.0 × ULN in the presence of documented Gilbert’s syndrome
- •- Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) =2.5 × ULN, or AST or ALT =5.0 × ULN in the presence of liver metastases
- •- Hematologic function:
- •a. Absolute neutrophil count =1000 cells/µL
- •b. Hemoglobin =8.5 g/dL or 5.28 mmol/L
- •c. Platelet count =75,000/µL
- •Significant cardiovascular disease, including:
- •- Cardiac failure New York Heart Association Class III or IV (Appendix D), or left ventricular ejection fraction (LVEF) <50% or below the lower limit of the
- •Institution’s normal range
- •- Myocardial infarction, severe or unstable angina within 6 months prior to baseline
- •- Significant thrombotic or embolic events within 3 months prior to baseline, including, but not limited to, stroke or transient ischemic attack. Catheterrelated thrombosis and deep vein thrombosis are not a cause for exclusion
- •- History or presence of any uncontrolled cardiovascular disease
- •- Personal or family history of long QT syndrome
- •Electrocardiogram (ECG) findings obtained using the study site’s ECG machine-derived measurements, meeting any of the following criteria:
- •- Evidence of second- or third-degree atrioventricular block
- •- Clinically significant arrhythmia (as determined by the Investigator)
- •- QTc interval of >470 msec as calculated according to Fridericia’s formula (QTcF = QT/R to R interval0.33)
- •Leptomeningeal or untreated central nervous system (CNS) malignancies (primary or metastatic); patients with asymptomatic CNS metastases who have undergone surgery or radiotherapy 4 weeks prior to Cycle 1 Day 1 and who are on a dose of prednisone of no more than 10 mg or equivalent will be eligible for Part A of the trial.
- •Taking or unable to discontinue proton pump inhibitors within 1 week prior to baseline
- •Known concurrent KRAS mutation
- •Known tumor-harboring resistance mutations including EGFR T790M or C797S mutations or HER2 C805S, T798I, or T862A mutations
- •Prior documented treatment response (i.e., complete response [CR], partial response [PR], or stable disease [SD] lasting =24 weeks by RECIST v1.1) to approved or investigational HER2 or EGFR therapies (e.g., afatinib, lapatinib, dacomitinib, neratinib, trastuzumab deruxtecan, poziotinib, mobocertinib, amivantamab)
- •- Patients with or without tumor response discontinuing after 8 weeks or less of therapy due to toxicity may be considered after discussion with the Sponsor Medical Monitor
- •- Patients with an NGS test (tissue or plasma) obtained within 8 weeks of Baseline which does not include any mutations listed in exclusion criteria #7
- •or #8 may be considered after discussion with the Sponsor Medical Monitor.
- •Women who are pregnant or breast-feeding
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