Phase 1b/2 Study of ATR InhibiTor RP-3500 and PARP Inhibitor Combinations in Patients With Molecularly Selected Cancers (ATTACC)
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 156
- 试验地点
- 13
- 主要终点
- Determine the Safety and Tolerability of Niraparib or Olaparib in Combination With RP-3500 in Patients With Molecularly Selected Solid Tumors
研究概览
简要总结
The primary purpose of this study is to assess the safety and tolerability of niraparib or olaparib in combination with RP-3500 (camonsertib), in patients with eligible advanced solid tumors, determine the maximum tolerated dose (MTD) of RP-3500 (camonsertib) in combination with niraparib or olaparib, examine pharmacokinetics (PK) and assess anti-tumor activity.
详细描述
This is a first-in-human Phase 1b/2, multi-center, open-label, dose-escalation and expansion study to:
- Evaluate the safety profile and MTD of RP-3500 (camonsertib) when administered orally in combination with niraparib or olaparib to establish the recommended Phase 2 dose and schedule.
- Characterize the PK profile of RP-3500 (camonsertib) in combination with niraparib or olaparib
- Assess anti-tumor activity associated with RP-3500 (camonsertib) in combination with niraparib or olaparib
- Examine biomarker responses and establish a correlation with RP-3500 (camonsertib) treatment in combination with niraparib or olaparib.
After the RP2D and schedule is determined, expansion cohort(s) for RP-3500 (camonsertib) in combination with niraparib or olaparib will be enrolled to study the anti-tumor effect, and further examine the safety, PK, and pharmacodynamic (PD).
Sponsor decided to terminate study early therefore, the Phase 2 expansion was not conducted
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
- •Male or female and ≥18 years-of-age at the time of signature of the informed consent
- •Confirmed advanced solid tumors resistant or refractory to standard treatment
- •Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0 or
- •Evaluable disease as per RECIST v1.1
- •Next generation sequencing (NGS) report obtained in CLIA-certified or equivalent laboratory demonstrating eligible tumor biomarkers.
- •Submission of available tumor tissue or willingness to have a biopsy performed if safe and feasible
- •Acceptable hematologic and organ function at screening
- •Negative pregnancy test for women of childbearing potential at Screening and prior to first study drug.
- •Ability to swallow and retain oral medications.
排除标准
- •Prior therapy with an ATR or DNA-dependent protein kinase (DNA-PK) inhibitor.
- •Chemotherapy, small molecule anticancer or biologic anticancer therapy given within 10 days or 5 half-lives (whichever is longer), prior to first dose of study drug.
- •Use of radiotherapy (except for palliative reasons) within 7 days 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.
- •No other anticancer therapy is to be permitted while the patient is receiving study treatment.
- •Major surgery ≤28 days or minor surgical procedures ≤7 days prior to first study treatment dose.
- •Uncontrolled, symptomatic brain metastases.
- •Uncontrolled high blood pressure
- •History of myelodysplastic syndrome (MDS) or acute myeloid leukemia (AML) diagnosis
- •Presence of other known active invasive cancers.
- •Pregnant or breastfeeding women.
- •Psychological, familial, sociological, or geographical conditions that do not permit compliance with the study protocol and/or follow-up procedures outlined in the protocol.
研究组 & 干预措施
Phase Ib Dose Escalation
Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with niraparib and/or Multiple dose levels of RP-3500 (camonsertib) for oral administration in combination with olaparib
干预措施: RP-3500 (camonsertib) (Drug)
Phase 2 Expansion Cohorts
Expansion cohort with RP-3500 (camonsertib) + niraparib and/or Expansion cohort RP-3500 (camonsertib) + olaparib
干预措施: RP-3500 (camonsertib) (Drug)
结局指标
主要结局
Determine the Safety and Tolerability of Niraparib or Olaparib in Combination With RP-3500 in Patients With Molecularly Selected Solid Tumors
时间窗: Start of treatment to 30 days post last dose, up to 23.7 months
Treatment Related Treatment-Emergent Adverse Events (TRAE) with ≥3 CTCAE Grade
Define the Recommended Phase 2 Dose (RP2D) of RP-3500 in Combination With Niraparib or Olaparib in Patients With Molecularly Selected Solid Tumors
时间窗: During 21 days (one cycle) from the initiation of the study treatment
Frequency of DLTs during the DLT observation period
次要结局
未报告次要终点