KontRASt-03: A Phase Ib/II, Multicenter, Open-label Platform Study of JDQ443 With Select Combinations in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 74
- 试验地点
- 17
- 主要终点
- Dose escalation: Frequency of dose interruptions and reductions, by treatment
研究概览
简要总结
This is Phase Ib/II, multicenter, open-label adaptive platform study of JDQ443 with select therapies in patients with advanced solid tumors harboring the KRAS G12C mutation.
详细描述
JDQ443 will be considered "backbone" treatment in this trial and combined with selected therapies, or "partner(s)". The combination of a backbone and a partner will constitute a treatment arm. After dose escalation, treatment arms that reach a maximum tolerated dose /recommended dose and are determined to be safe may, but are not required to, proceed to Phase II to further explore safety, tolerability, and anti-tumor activity.
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 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Dose Escalation:
- •- Patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care therapy or are ineligible to receive such therapy.
- •Patients with advanced (metastatic or unresectable) KRAS G12C mutant non-small cell lung cancer who have received platinum-based chemotherapy regimen and immune checkpoint inhibitor therapy, unless patient was ineligible to receive such therapy
- •Patients with advanced (metastatic or unresectable) KRAS G12C mutant colorectal cancer who have received fluropyrimidine-, oxaliplatin-, and irinotecan-based chemotherapy, unless patient was ineligible to such therapy.
- •All patients:
- •ECOG performance status of 0 or
- •Patients must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution's guidelines.
排除标准
- •Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
- •Prior treatment with a KRAS G12C inhibitor is excluded for patients in a subset of groups in Phase II.
- •Active brain metastases, including symptomatic brain metastases or known leptomeningeal disease
- •Clinically significant cardiac disease or risk factors at screening
- •Insufficient bone marrow, hepatic or renal function at screening Other protocol-defined inclusion/exclusion criteria may apply
研究组 & 干预措施
JDQ443+trametinib
JDQ443 in combination with trametinib
干预措施: JDQ443 (Drug)
JDQ443+trametinib
JDQ443 in combination with trametinib
干预措施: trametinib (Drug)
JDQ443+ribociclib
JDQ443 in combination with ribociclib
干预措施: JDQ443 (Drug)
JDQ443+ribociclib
JDQ443 in combination with ribociclib
干预措施: Ribociclib (Drug)
JDQ443+cetuximab
JDQ443 in combination with cetuximab
干预措施: JDQ443 (Drug)
JDQ443+cetuximab
JDQ443 in combination with cetuximab
干预措施: cetuximab (Biological)
结局指标
主要结局
Dose escalation: Frequency of dose interruptions and reductions, by treatment
时间窗: 24 months
The number of patients with dose adjustments (reductions and interruptions) will be summarized by treatment group.
Dose escalation: Incidence and severity of dose limiting toxicities (DLTs) of each combination treatment.
时间窗: 28 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value that is not primarily related to disease, disease progression, intercurrent illness/injury, or concomitant medications that occurs within the first 28 days of study treatment and meets a defined criteria.
Dose Escalation: Dose intensity by treatment
时间窗: 24 months
Dose intensity is defined as the ratio of actual cumulative dose received and actual duration of response.
Dose escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment
时间窗: 24 months
All information obtained on AE will be displayed by treatment group. Summary tables will include only AEs that started/worsened during the cycles of treatment (treatment-emergent AEs).
PhaseII: Overall Response Rate by Blinded Independent Review Committee (BIRC) per RECIST 1.1
时间窗: 24 months
ORR is the proportion of patients with a best overall response (BOR) of Complete Response (CR) or Partial Response (PR).
次要结局
- Dose escalation and Phase II: Duration of Response (DoR) by local review per RECIST 1.1(24 months)
- Dose escalation and Phase II: Disease Control Rate (DCR) by local review per RECIST 1.1(24 months)
- Dose escalation and Phase II: Progression-Free Survival (PFS) by local review per RECIST 1.1(24 months)
- Dose escalation and Phase II: PK parameters - Maximum Concentration (Cmax), as applicable per arm(5 months)
- Phase II: Overall survival (OS)(24 months)
- Dose escalation and Phase II: ORR by local review per RECIST 1.1(24 months)
- Phase II: DoR by BIRC per RECIST 1.1(24 months)
- Dose escalation and Phase II: PK parameters - Minimum Concentration (Cmin), as applicable per arm(5 months)
- Phase II: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs) by treatment(24 months)
- Phase II: DCR by BIRC per RECIST 1.1(24 months)
- Dose escalation: Time to achieve Cmax - Tmax, as applicable per arm(5 months)
- Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCtau, as applicable per arm(5 months)
- Dose escalation and Phase II: Plasma or serum concentration vs time profiles - AUCinf, as applicable per arm(5 months)
- Phase II: Frequency of dose interruptions and reductions, by treatment(24 months)
- Phase II: Dose intensity by treatment(24 months)
- Phase II: PFS by BIRC per RECIST 1.1(24 months)