Phase 1 Study of the PKMYT1 Inhibitor RP-6306 in Combination With Gemcitabine for the Treatment of Advanced Solid Tumors (MAGNETIC Study)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 67
- 试验地点
- 11
- 主要终点
- Number of Dose Limiting Toxicities, as Defined Per Protocol, That Occur During the First Cycle (21 Days) of Treatment at Each Dose Level
研究概览
简要总结
The primary purpose of this study is to assess the safety and tolerability of RP-6306 in combination gemcitabine, in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-6306 in combination with gemcitabine, identify a recommended phase 2 dose (RP2D) and preferred schedule, examine preliminary pharmacokinetics (PK) and assess anti-tumor activity.
详细描述
Phase 1, multi-center, open-label, dose-escalation study to:
- Evaluate the safety profile and MTD of RP-6306 with gemcitabine to establish the RP2D and schedule
- Characterize the PK and pharmacodynamics of RP-6306 with gemcitabine
- Assess preliminary anti-tumor activity associated with RP-6306 with gemcitabine
The Sponsor of the study has changed from 'Repare Therapeutics' to 'Debiopharm International SA' in the United States.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Male or female and ≥18 years-of-age at the time of informed consent.
- •ECOG Performance status 0 or
- •Locally advanced or metastatic resistant or refractory solid tumors.
- •Submission of available tumor tissue at screening or willingness to have a biopsy performed if safe and feasible.
- •Measurable disease as per RECIST v1.
- •Ability to swallow and retain oral medications.
- •Acceptable hematologic and organ function at screening.
- •Negative pregnancy test (serum) for women of childbearing potential (WOCBP) at Screening.
- •Resolution of all toxicities of prior therapy or surgical procedures.
- •Life expectancy ≥12 weeks after the start of the treatment
排除标准
- •Chemotherapy or small molecule antineoplastic agent given within 21 days or <5 half- lives, whichever is shorter, prior to first dose of study drug.
- •History or current condition, therapy, or laboratory abnormality that might confound the study results or interfere with the patient's participation for the full duration of the study treatment.
- •Patients who are pregnant or breastfeeding.
- •Known sensitivity to any of the ingredients of RP-6306 or gemcitabine.
- •Life-threatening illness, medical condition, active uncontrolled infection, or organ system dysfunction or other reasons which, in the investigator's opinion, could compromise the participating patient's safety.
- •Major surgery within 4 weeks prior to first dose of RP-6306 and gemcitabine.
- •Uncontrolled, symptomatic brain metastases.
- •Uncontrolled hypertension.
- •Moderate or severe hepatic impairment
- •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol and/or follow-up procedures outlined in the protocol.
研究组 & 干预措施
Phase 1 Dose Escalation
Multiple dose levels of RP-6306 and gemcitabine
干预措施: RP-6306 (oral PKMYT1 inhibitor) (Drug)
结局指标
主要结局
Number of Dose Limiting Toxicities, as Defined Per Protocol, That Occur During the First Cycle (21 Days) of Treatment at Each Dose Level
时间窗: During 21 days from the initiation of the study treatment (C1D1)
Evaluation of dose-limiting toxicities (DLTs) at or below a frequency of 25%
Number of Patients With of Treatment-related Adverse Event Data Per CTCAE v5.0 Criteria to Determine Safety and Tolerability of RP-6306 in Combination With Gemcitabine.
时间窗: Start of treatment to 30 days post last dose. up to 1.5 years
Incidence of grade 3 and above Treatment Related Emergent Adverse Events (TRAEs)
次要结局
未报告次要终点