Phase 1b/2 Safety, Pharmacokinetic, and Efficacy Study of G1T38 in Combination With Osimertinib in Patients With EGFR Mutation-Positive Metastatic Non-Small Cell Lung Cancer (NSCLC)
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 30
- 试验地点
- 8
- 主要终点
- Dose Limiting Toxicity
研究概览
简要总结
This was a study to investigate the potential clinical benefit of G1T38 as an oral therapy in combination with osimertinib in patients with EGFR mutation-positive metastatic non-small cell lung cancer.
The study was an open-label design, planned to consist of 2 parts: a safety, pharmacokinetic, and dose-finding portion (Part 1), and a randomized portion (Part 2). Both parts were to include 3 study phases: Screening Phase, Treatment Phase, and Survival Follow-up Phase. The Treatment Phase began on the day of first dose with study treatment and completes at the Post-Treatment Visit. Approximately, 144 patients were planned to be enrolled in the study.
详细描述
Part 2, the Phase 2 part of the study, was not conducted due to changes in corporate strategy. There were no safety signals identified in Phase 1/Part 1 that would have precluded the conduct of Part 2. As a result, 30 out of the planned 144 patients were enrolled.
All tumor assessments were conducted by the Investigators or site radiologist. In order to reduce the burden to the patients, data of overall survival (OS) were no longer required (since 29 January 2020). No OS analysis was conducted for Part 1 due to limited data in Part 1.
PK data for Cohorts 4 (150 BID) and 5 (200 BID) were not analyzed as they were deemed unnecessary, as the PK data from Cohorts 1-3 were sufficient to achieve the secondary study objective of assessing the effect of osimertinib on PK parameters of G1T38.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 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
- •Confirmed EGFR mutation for non-small cell lung cancer associated with EGFR TKI sensitivity
- •For Part 2, EGFR T790M mutation-positive tumor status
- •Left ventricular ejection fraction (LVEF) ≥ institution's lower limit of the reference range
- •For Part 1, evaluable or measurable disease as defined by RECIST, Version 1.1
- •For Part 2, measurable disease as defined by RECIST, Version 1.1
- •ECOG performance status 0 to 1
- •Adequate organ function
排除标准
- •Prior treatment with EGFR TKI within 9 days of first study dose
- •For Part 1, prior treatment with more than 2 prior lines of chemotherapy for advanced NSCLC
- •For Part 2, prior treatment with osimertinib or other T790M active EGFR TKI
- •For Part 2, prior chemotherapy for advanced NSCLC
- •Active uncontrolled/symptomatic CNS metastases, carcinomatous meningitis, or leptomeningeal disease
- •Investigational drug within 3 months or 5 half-lives, whichever is longer, of first study dose
- •Concurrent radiotherapy, radiotherapy within 28 days of first study dose, previous radiotherapy to the target lesion sites, or prior radiotherapy to > 25% of bone marrow
- •Prior hematopoietic stem cell or bone marrow transplantation
研究组 & 干预措施
Part 1: Cohort 1 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: G1T38 (Drug)
Part 1: Cohort 1 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: Osimertinib (Drug)
Part 1: Cohort 2 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: G1T38 (Drug)
Part 1: Cohort 2 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: Osimertinib (Drug)
Part 1: Cohort 3 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: G1T38 (Drug)
Part 1: Cohort 3 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: Osimertinib (Drug)
Part 1: Cohort 4 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: G1T38 (Drug)
Part 1: Cohort 4 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: Osimertinib (Drug)
Part 1: Cohort 5 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: G1T38 (Drug)
Part 1: Cohort 5 G1T38 + Osimertinib
Patients will receive a single oral dose of G1T38 on Cycle 1 Day -16 and on Cycle 1 Day -2. Patients will receive oral osimertinib 80 mg beginning Cycle 1 Days -14. Patients will begin G1T38 once-daily dosing on Cycle 1 Day 1 (in combination with osimertinib 80 mg).
干预措施: Osimertinib (Drug)
结局指标
主要结局
Dose Limiting Toxicity
时间窗: Cycle 1 Day -16 to Cycle 1 Day 28
The percentage of patients experiencing DLTs in Part 1 of the study in each cohort, including: * Grade 4 neutropenia * ≥ Grade 3 neutropenic infection/febrile neutropenia * Grade 4 thrombocytopenia * ≥ Grade 3 thrombocytopenia with bleeding * ≥ Grade 3 nonhematologic toxicity (additional criteria for nausea, vomiting, diarrhea, or fatigue: lasting \> 5 days with maximal medical management) * Liver function test abnormalities meeting Hy's Law criteria (aspartate aminotransferase \[AST\] or alanine aminotransferase \[ALT\] ≥ 3 × upper limit of normal \[ULN\] and total bilirubin ≥ 2 × ULN).
次要结局
- Progression Free Survival (PFS)(36 months)
- Best Overall Tumor Response(21 months)
- Pharmacokinetics of G1T38 and Metabolite G1T30: Maximum Plasma Concentration (Cmax)(Part 1, Cycle 1 Day -16 to Day -2.)
- Pharmacokinetics of G1T38 and Metabolite G1T30: Area Under Curve - Plasma Concentration (AUC) Infinity(Part 1, Cycle 1 Day -16 to Day -2.)
- Pharmacokinetics of G1T38 and Metabolite G1T30: Plasma: Terminal Half Life (T1/2)(Part 1, Cycle 1 Day -16 to Day -2.)
- Pharmacokinetics of G1T38: Plasma - Volume of Distribution(Part 1, Cycle 1 Day -16 to Day -2.)