Phase 1 Trial of the Safety, Pharmacokinetics, Pharmacodynamics, and Preliminary Clinical Activity of RP-3467 Alone and in Combination With Olaparib in Participants With Advanced Solid Tumors (POLAR Trial)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 26
- 试验地点
- 10
- 主要终点
- The Number of Participants Who Experienced Dose-limiting Toxicities (DLT) During the Study Treatment
研究概览
简要总结
This is a multicenter, open-label Phase 1 trial to investigate the safety, PK, and pharmacodynamics of the Polθ inhibitor RP-3467 alone or in combination with the poly-ADP ribose polymerase inhibitor (PARPi) olaparib in adults with molecularly selected advanced solid tumors.
详细描述
This is a first-in-human Phase 1, multi-center, open-label, dose-escalation study to:
- Evaluate the safety profile of RP-3467 when administered orally alone and in combination with olaparib and to define the MTD or MAD for RP-3467 monotherapy and the RP2D for the combination
- Characterize the PK profile of RP-3467 alone and in combination with olaparib
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
- •Male or female participants ≥18 years of age at the time of signing the informed consent
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- •Participant must have one of the following that has progressed or was non-responsive to prior systemic therapy and for which no standard or available known therapeutic option exists:
- •locally advanced or metastatic epithelial ovarian cancer (including fallopian tube or primary peritoneal), or
- •metastatic breast cancer, or
- •metastatic castration-resistant prostate cancer (mCRPC), or
- •pancreatic adenocarcinoma
- •Measurable disease per RECIST v1.1 (exceptions for participants with non-measurable but evaluable disease [per RECIST and or PSA/CA-125])
- •Next generation sequencing (NGS) report demonstrating eligible tumor biomarker
- •Provision of archival tumor tissue, or if adequate archival tumor tissue is not available, provision of a fresh biopsy if there is a lesion that can be safely biopsied
- •Acceptable organ function at Screening
- •Acceptable hematologic function at Screening
- •Life expectancy ≥12 weeks after the start of the treatment according to the Investigator's judgment
排除标准
- •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.
- •Uncontrolled, symptomatic brain metastases.
- •Presence of other known active invasive cancers
- •History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
- •Prior therapy with a Polθ inhibitor other than RP-3467
研究组 & 干预措施
Arm 1: RP-3467 monotherapy
Eligible participants will be treated with escalating doses of RP-3467 monotherapy
干预措施: RP-3467 at assigned dose and schedule (Drug)
Arm2: RP-3467 + Olaparib combination
Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib
干预措施: RP-3467 at assigned dose and schedule (Drug)
Arm2: RP-3467 + Olaparib combination
Eligible participants will be treated with escalating doses of RP-3467 in combination with Olaparib
干预措施: Olaparib 200-300 mg BID, daily (Drug)
结局指标
主要结局
The Number of Participants Who Experienced Dose-limiting Toxicities (DLT) During the Study Treatment
时间窗: Start of treatment to 30 days post last dose, up to 13 months
The assessment of DLTs was conducted to evaluate the safety and tolerability of RP-3467 administered as monotherapy and in combination with olaparib in participants with advanced solid tumors.
次要结局
未报告次要终点