A Modular, Open-label, Phase I/II Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Efficacy of EP0031 in Patients With Advanced RET-altered Malignancies
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 发起方
- 入组人数
- 265
- 试验地点
- 79
- 主要终点
- Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment
研究概览
简要总结
The aim of this study is to assess the safety, side effects and effectiveness of EP0031 (Lunbotinib) in patients with advanced RET-altered non-small cell lung cancer (NSCLC) in monotherapy and in combination with standard of care (SOC) chemotherapy.
详细描述
EP0031 is being investigated in this modular, interventional Phase I/II dose escalation and dose expansion study to investigate the optimal dose in adult patients with advanced RET-altered NSCLC. Currently there are no approved RET-targeted treatments for patients who progress on first-generation Selective RET Inhibitors (SRIs). However, it is proposed that EP0031 can overcome resistance mechanisms to first generation SRIs, as EP0031 is a potent and selective RET inhibitor with broad activity against common RET fusions and mutations. Phase I (dose escalation and optimization) has completed for this study and determined the Recommended Phase 2 Dose (RP2D). The study is now in Phase 2, assessing the safety, tolerability and efficacy of EP0031 given in combination with SOC chemotherapy in RET fusion positive NSCLC participants.
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
- •Applicable to all participants:
- •Must be ≥18 years of age, with documented RET-altered NSCLC
- •Participants should be well informed and consented about alternative treatment options including approved RET-targeted therapies
- •ECOG performance status of 0 or 1 and life expectancy >3 months at screening
- •Ability to understand and provide written informed consent and able to participate in all required evaluations and procedures
- •Measurable disease defined by RECIST v1.1
- •Must have locally advanced or metastatic NSCLC with RET fusion who are eligible to receive platinum-based doublet chemotherapy.
- •First line patients: Must not have received a Selective RET inhibitor or chemotherapy. Prior adjuvant and neo-adjuvant therapies (chemotherapy, radiotherapy, immunotherapy, biologic therapy, investigational agents), or definitive radiation/chemoradiation with or without regimens including immunotherapy, biologic therapy, investigational agents, are permitted as long as treatment was completed at least 12 months prior. Palliative radiotherapy for symptom management (eg, bone metastases) is permitted up to 2 weeks prior to treatment start.
排除标准
- •Participants with any of the following will not be included in the study:
- •Any known major driver gene alterations other than RET.
- •Spinal cord compression or brain metastases. Patients with stable brain metastases can be enrolled.
- •Active infection requiring systemic antibiotic, antifungal, or antiviral medication
- •Severe or uncontrolled medical condition or psychiatric condition
- •Chronic glomerulonephritis or renal transplant
- •Participants with active hepatitis B infection or active hepatitis C
- •Participants with active HIV infection. Patients living with HIV may be eligible if they have adequate CD4+ T-cell count and no history of AIDS-defining opportunistic infections in the past 12 months
- •Receipt of any strong inhibitor or inducer of CYP3A4
- •Impaired hepatic or renal function, inadequate bone marrow reserve or organ function
- •Any clinically important abnormalities in rhythm, conduction, or morphology on resting ECG or any factor that increases the risk of QTc prolongation or of arrhythmic events , or congestive heart failure Grade III-IV according to the New York Heart Association, myocardial infarction, or unstable angina within the previous 6 months
- •Uncontrolled hypertension
- •Corneal ulceration or untreated keratitis at screening
研究组 & 干预措施
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
Cohort for eligible patients with no prior first line treatment with a 1st gen SRI or chemotherapy.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: EP0031 (Drug)
RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy
Cohort for eligible patients treated previously with a 1st gen SRI.
COHORT IS NOW CLOSED TO RECRUITMENT.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: Pemetrexed (Drug)
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
Cohort for eligible patients with no prior first line treatment with a 1st gen SRI or chemotherapy.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: Platinum chemotherapy (Drug)
RET fusion-positive NSCLC (treatment naïve i.e. no prior therapy) in combination w/ SOC chemotherapy
Cohort for eligible patients with no prior first line treatment with a 1st gen SRI or chemotherapy.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: Pemetrexed (Drug)
RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy
Cohort for eligible patients treated previously with a 1st gen SRI.
COHORT IS NOW CLOSED TO RECRUITMENT.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: EP0031 (Drug)
RET fusion-positive NSCLC (post-SRI) in combination w/ SOC chemotherapy
Cohort for eligible patients treated previously with a 1st gen SRI.
COHORT IS NOW CLOSED TO RECRUITMENT.
EP0031 capsules at the recommended dose, taken once daily, in combination with doublet platinum-based SOC chemotherapy, both administered on Day 1 of 21-day cycles for 4 cycles, followed by EP0031 plus pemetrexed maintenance until progressive disease (PD), unacceptable toxicity or patient withdrawal
干预措施: Platinum chemotherapy (Drug)
结局指标
主要结局
Module A: Incidence of Dose-limiting Toxicity (DLTs ) during the first 28 days of EP0031 treatment
时间窗: First 28 days of treatment
Modules B and C: Overall Response Rate (ORR) as measured using RECIST v1.1
时间窗: 12 months
Module B: Incidence of Dose-limiting Toxicity (DLTs ) during the first 21 days of EP0031 given in combination with SOC chemotherapy treatment
时间窗: First 21 days of treatment
次要结局
- Area under the plasma concentration versus time curve (AUC)(First 48 hours after drug administered)
- Maximum Plasma Concentration (Cmax)(First 24 hours after drug administered)
- Time taken for drug concentration to fall from half its original value (Half-life)(First 72 hours after drug administered)
- Module B: Overall Response Rate (ORR) as measured using RECIST v1.1(12 months)
- Area under the plasma concentration versus time curve (AUC)(First 24 hours after drug administered)
- Time taken for drug concentration to fall from half its original value (Half-life)(First 24 hours after drug administered)