Phase 1 Study of Tipifarnib and Osimertinib in EGFR-mutated Non-Small Cell Lung Cancer
试验速览
- 阶段
- 1 期
- 状态
- 撤回
- 试验地点
- 2
- 主要终点
- For Dose Expansion characterize the safety profile of tipifarnib in combination with osimertinib as per NCI CTCAE v5.0 using descriptive statistics of adverse events
研究概览
简要总结
This is a Phase 1a/b, multicenter, open-label, dose escalation (1a) and dose expansion (1b) study. The purpose of this study is to measure safety, tolerability, and preliminary efficacy with the combination of tipifarnib with osimertinib in patients with advanced/metastatic EGFR-mutated non-small cell lung cancer.
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
- •Age ≥ 18 years at the time of signing informed consent.
- •Histologically or cytologically confirmed stage IIIB (locally-advanced) or IV (metastatic) adenocarcinoma of the lung.
- •The tumor harbors an Ex19del or Ex21-L858R substitution (based on tumor tissue or plasma [ctDNA] assessment).
- •Treatment-naïve for locally advanced/metastatic EGFR-mutated NSCLC and osimertinib treatment-naïve for NSCLC.
- •ECOG performance score of 0 or 1 with no clinically significant deterioration over the previous 2 weeks and a minimum life expectancy of 12 weeks.
- •Measurable disease by RECIST v1.1 that meets the criteria for selection as a target lesion according to RECIST v1.
- •Adequate organ function, as evidenced by the laboratory results.
- •Other protocol-defined inclusion criteria may apply.
排除标准
- •Treatment with any of the following:
- •Major surgery
- •Radiotherapy treatment to more than 30% of the bone marrow or with a wide field of radiation within 4 weeks of the first dose of study drug
- •Medications or herbal supplements known to be potent inhibitors or inducers of cytochrome P450 (CYP) 3A4 or uridine 5'-diphospho (UDP)-glucuronosyltransferase (UGT), or inhibitors of breast cancer resistance protein (BCRP).
- •Investigational therapy within 2 weeks of Cycle 1 Day 1
- •Concurrent and/or other active malignancy that has required systemic treatment within 2 years of first dose of study drug (excluding non-melanoma skin cancer, adjuvant hormonal therapy for breast cancer and hormonal treatment for castration-sensitive prostate cancer)
- •Spinal cord compression or symptomatic and unstable brain metastases requiring steroids over the last 4 weeks prior.
- •Evidence of severe or uncontrolled systemic diseases.
- •Refractory nausea and vomiting, chronic gastrointestinal (GI) diseases, inability to swallow the formulated product, or previous significant bowel resection.
- •Clinically significant cardiovascular symptoms or disease.
- •Received treatment for unstable angina within prior year, myocardial infarction within the prior 6 months, cerebro-vascular attack within the prior year, history of New York Heart Association grade III or greater congestive heart failure, or current serious cardiac arrhythmia requiring medication except atrial fibrillation.
- •Past medical history of Interstitial Lung Disease (ILD), drug induced ILD, radiation pneumonitis which required steroid treatment, or any evidence of clinically active ILD.
- •Other protocol-defined exclusion criteria may apply.
研究组 & 干预措施
Escalation Cohort
Adult participants with EGFR-mutated Non-Small Cell Lung Cancer
干预措施: Tipifarnib (Drug)
Escalation Cohort
Adult participants with EGFR-mutated Non-Small Cell Lung Cancer
干预措施: Osimertinib (Drug)
Expansion Cohort
Adult participants with EGFR-mutated Non-Small Cell Lung Cancer
干预措施: Tipifarnib (Drug)
Expansion Cohort
Adult participants with EGFR-mutated Non-Small Cell Lung Cancer
干预措施: Osimertinib (Drug)
结局指标
主要结局
For Dose Expansion characterize the safety profile of tipifarnib in combination with osimertinib as per NCI CTCAE v5.0 using descriptive statistics of adverse events
时间窗: Through study completion, an average of 2 years
Descriptive statistics of adverse events per the NCI CTCAE v5.0
For Dose Escalation determine a safe and tolerable Phase 2 dose of tipifarnib when used in combination with osimertinib
时间窗: At the end of Cycle 1 (each cycle is 28 days)
Occurrence of DLTs during first treatment cycle
For Dose Escalation characterize the safety of the combination DLTs will be listed for patients who complete the evaluation period for DLT
时间窗: DLTs will be evaluated at the end of cycle 1 (28 days), but also through study completion, an average of 1.5 years
Descriptive statistics of adverse events per NCI Common Terminology Criteria for Adverse Events (CTCAE v5.0)
For Dose Expansion characterize the safety profile of tipifarnib in combination with osimertinib as per NCI CTCAE v5.0 using the percentage of patients who discontinue the combination for related adverse events
时间窗: First 6 cycles of treatment (28 day treatment cycle)
Percentage of patients who discontinue the combination for tipifarnib and/or osimertinib related adverse events prior to completing 6 cycles of treatment
次要结局
- To evaluate the efficacy of tipifarnib in combination with osimertinib(Assessed every 8 weeks for the first year and every 12 weeks thereafter up to end of study at approximately 2 years)
- To study pharmacokinetics (PK) of tipifarnib and osimertinib in combination(Cycles 1-6 (28 day treatment cycle))
- To evaluate circulating tumor DNA (ctDNA) as an indicator or response in both ctDNA positive and negative patients by changes in genetic alterations(Monthly for duration of trial participation (an average of 2 years))
- To evaluate circulating tumor DNA (ctDNA) clearance rates for patients positive at baseline(Monthly for duration of trial participation (an average of 2 years))
- To evaluate circulating tumor DNA (ctDNA) time to detection changes associated with disease progression(Monthly for duration of trial participation (an average of 2 years))