A Phase 1/2, Open-Label, Multi-Center Study of ZN-c3 Administered in Combination With Encorafenib and Cetuximab in Adults With Metastatic Colorectal Cancer
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 发起方
- 入组人数
- 44
- 试验地点
- 27
- 主要终点
- Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)
研究概览
简要总结
The purpose of this study is to evaluate the safety, tolerability, and potential clinical benefits of ZN-c3 administered in combination with encorafenib and cetuximab in adult participants with metastatic BRAF V600E mutant colorectal cancer previously treated with one or two treatment regimens.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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
- •Histologically or cytologically confirmed metastatic Stage IV colorectal adenocarcinoma.
- •Documented evidence of a BRAF V600E mutation in tumor tissue or blood
- •Presence of measurable disease per RECIST version 1.1 guidelines.
- •Disease progression after 1 or 2 previous systemic regimens for metastatic disease
- •Adequate bone marrow function
- •Adequate hepatic and renal function
排除标准
- •Documented clinical disease progression or radiographic disease progression during the screening period
- •Leptomeningeal disease.
- •Symptomatic brain metastasis.
- •Presence of acute or chronic pancreatitis.
- •Unable to swallow, retain, and absorb oral medications.
- •Clinically significant cardiovascular diseases
- •Evidence of active noninfectious pneumonitis.
- •Evidence of active and uncontrolled bacterial or viral infection, within 2 weeks prior to start of any of the study interventions
- •Participants with known positivity for HIV
- •Active hepatitis B or hepatitis C infection
- •Concurrent or previous other malignancy within 2 years of study entry
- •Has had an allogeneic tissue/solid organ transplant
- •Pregnant or females of childbearing potential who have a positive β-hCG laboratory test result within 14 days prior to enrollment or is breastfeeding
研究组 & 干预措施
Dose Escalation
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
干预措施: ZN-c3 (Drug)
Dose Escalation
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
干预措施: Encorafenib (Drug)
Dose Escalation
Participants will receive different doses of ZN-c3 in combination with different doses of Encorafenib and a fixed dose of Cetuximab
干预措施: Cetuximab (Drug)
Dose Expansion
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
干预措施: ZN-c3 (Drug)
Dose Expansion
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
干预措施: Encorafenib (Drug)
Dose Expansion
Participants will receive recommended dose of ZN-c3 and encorafenib as determined in dose escalation phase in combination with cetuximab
干预措施: Cetuximab (Drug)
结局指标
主要结局
Dose Escalation Phase - Incidence of Dose Limiting Toxicities (DLTs)
时间窗: From Lead-in Day -1 to Cycle 1 Day 28
DLTs defined as treatment-related AEs occurring within the first 29 days after the start of any study treatment that in the opinion of the investigator cannot be reasonably attributed to the participant's underlying disease, concomitant medications, or pre-existing conditions.
Dose Expansion Phase - Objective response rate (ORR)
时间窗: From first dose of any study intervention every 8 weeks during treatment, up to 12 months
ORR defined as the proportion of participants who achieves a best overall response of Complete Response (CR) or Partial Response (PR), assessed by Investigator per RECIST Version 1.1.
次要结局
- Dose Escalation Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Cmax(Cycle 1 Day 15)
- Proportion of participants with dose interruptions due to AEs in Dose Escalation Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Proportion of participants with dose modifications due to AEs in Dose Escalation Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Proportion of participants with discontinuations due to AEs in Dose Escalation Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Dose Escalation Phase - Objective response rate (ORR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Escalation Phase - Duration of Response (DOR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Escalation Phase - Progression Free Survival (PFS)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Escalation Phase - Disease Control Rate (DCR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Escalation Phase - Time to Response (TTR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Escalation - ZN-c3 plasma exposure: AUC(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Escalation - ZN-c3 plasma exposure: Cmax(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Escalation - ZN-c3 plasma exposure: Tmax(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Escalation - Encorafenib plasma exposure: AUC(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Escalation - Encorafenib plasma exposure: Cmax(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Escalation - Encorafenib plasma exposure: Tmax(From lead in day -1 visit through Cycle 1 Day 15)
- Dose Expansion Phase - Duration of Response (DOR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Expansion Phase - Progression Free Survival (PFS)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Expansion Phase - Disease Control Rate (DCR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Expansion Phase - Time to Response (TTR)(From first dose of any study intervention every 8 weeks during treatment, up to 12 months)
- Dose Expansion Phase - Incidence and severity of adverse events (AEs) as assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Proportion of participants with dose interruptions due to AEs in Dose Expansion Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Proportion of participants with dose modifications due to AEs in Dose Expansion Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Proportion of participants with discontinuations due to AEs in Dose Expansion Phase(From first dose of any study intervention through 28 days after the last dose of any study intervention)
- Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: AUC(Lead in day 7)
- Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Cmax(Lead in day 7)
- Dose Expansion - ZN-c3 in combination with combination with E+C plasma exposure: Tmax(Day 7)
- Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: AUC(Cycle 1 Day 15)
- Dose Expansion - Encorafenib in combination with ZN-c3 and cetuximab plasma exposure: Tmax(Cycle 1 Day 15)
- Dose Expansion - ZN-c3 plasma exposure: AUC(Cycle 1 Day 15)
- Dose Expansion - ZN-c3 plasma exposure: Cmax(Cycle 1 Day 15)
- Tumor tissue BRAF V600E mutational status(From lead in day 1 visit through the last dose of any study intervention, up to 12 months)