A Phase 1, Open-Label, Multicenter, Dose-Escalation Study of RMC-4630 Monotherapy in Adult Participants With Relapsed/Refractory Solid Tumors
试验速览
- 阶段
- 1 期
- 入组人数
- 133
- 试验地点
- 12
- 主要终点
- Number of participants with adverse events (AEs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetic (PK), and pharmacodynamic (PD) profiles of escalating doses of RMC-4630 monotherapy in adult participants with relapsed/refractory solid tumors and to identify the recommended Phase 2 dose (RP2D).
详细描述
This is an open-label, multicenter, Phase 1 study of oral RMC-4630 monotherapy in participants with advanced relapsed or refractory solid tumors. The study will include 2 components: 1) a Dose-Escalation Component for participants with relapsed or refractory solid tumors and 2) a Dose-Expansion Component for participants with relapsed or refractory solid tumors harboring certain specific mutations/rearrangements that result in hyperactivation of the RAS-MAPK pathway. Participants will be treated until disease progression per RECIST v1.1, unacceptable toxicity, or other criteria for withdrawal are met, whichever occurs first.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 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
- •Participant (male or female) ≥18 years of age
- •Participants who have advanced solid tumors that have failed, are intolerant to, or are considered ineligible for standard of care anticancer treatments including approved drugs for oncogenic drivers in their tumor type
- •Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
- •Participants in the Dose-Expansion Component must have one of the following genotypic aberrations: KRAS amplifications, KRASG12C (NSCLC), BRAF Class 3, or NF1 LOF (NSCLC and gynecological cancers) mutations
- •Adequate hematologic, hepatic and renal function
- •Participant able to understand and voluntarily sign the informed consent form (ICF) and able to comply with the study visit schedule and other protocol requirements.
- •Participants willing to agree to not father a child/become pregnant and comply with effective contraception criteria
排除标准
- •Known or suspected leptomeningeal or brain metastases or spinal cord compression
- •Primary central nervous system (CNS) tumors
- •Clinically significant cardiac disease
- •Active, clinically significant interstitial lung disease or pneumonitis
- •History or current evidence of retinal pigment epithelial detachment (RPED), central serous retinopathy, retinal vein occlusion (RVO), or predisposing factors to RPED or RVO
- •Known HIV infection
- •Active/chronic hepatitis B or C infection
- •Any other unstable or clinically significant concurrent medical condition that would, in the opinion of the investigator, jeopardize the safety of a participant, impact their expected survival through the end of the study participation, and/or impact their ability to comply with the protocol prior/concomitant therapy
- •Females who are pregnant or breastfeeding
研究组 & 干预措施
RMC-4630
RMC-4630 for oral administration
干预措施: RMC-4630 (Drug)
结局指标
主要结局
Number of participants with adverse events (AEs)
时间窗: up to 3 years
Incidence, nature, and severity of treatment-emergent AEs and serious AEs, including incidence and severity of findings in laboratory values and vital signs for RMC-4630 monotherapy
Number of participants with dose limiting toxicities (DLTs)
时间窗: 28 days
Incidence and nature of DLTs with RMC-4630 monotherapy
次要结局
- Cmax(up to 3 years)
- Tmax(up to 3 years)
- Area Under the Curve (AUC)(up to 3 years)
- t1/2(up to 3 years)
- Accumulation Ratio(up to 3 years)
- Overall Response Rate (ORR)(up to 3 years)
- Duration of Response (DOR)(up to 3 years)