A Phase Ib/II Open-label, Multi-center Dose Escalation Study of JDQ443 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
- 344
- 试验地点
- 38
- 主要终点
- Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
研究概览
简要总结
This is a phase Ib/II open label study. The escalation part will characterize the safety and tolerability of JDQ443 single agent and JDQ443 in combination with the other study treatments (TNO155 and tislelizumab) in advanced solid tumor patients. After the determination of the maximum tolerated dose / recommended dose for a particular treatment arm, dose expansion will assess the anti-tumor activity and further assess the safety, tolerability, and PK/PD of each regimen at the maximum tolerated dose / recommended dose or lower dose.
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
- •Adult patients with advanced (metastatic or unresectable) KRAS G12C mutant solid tumors who have received standard of care or are intolerant or ineligible to approved therapies
- •ECOG Performance Status of 0 or 1
- •At least one measurable lesion as defined by RECIST 1.1
- •Prior treatment with a KRAS G12C inhibitor may be allowed for dose escalations of combinations and a subset of groups in dose expansion
排除标准
- •Tumors harboring driver mutations that have approved targeted therapies, with the exception of KRAS G12C mutations
- •Symptomatic brain metastases or known leptomeningeal disease. Patients with asymptomatic treated or untreated brain metastases may be eligible
- •Clinically significant cardiac disease or risk factors at screening
- •A medical condition that results in increased photosensitivity Other protocol-defined inclusion/exclusion criteria may apply.
研究组 & 干预措施
Arm A
JDQ443
干预措施: JDQ443 (Drug)
Arm B
JDQ443 in combination with TNO155
干预措施: JDQ443 (Drug)
Arm B
JDQ443 in combination with TNO155
干预措施: TNO155 (Drug)
Arm C
JDQ443 in combination with tislelizumab
干预措施: JDQ443 (Drug)
Arm C
JDQ443 in combination with tislelizumab
干预措施: tislelizumab (Biological)
Arm D
JDQ443 in combination with TNO155 and tislelizumab
干预措施: JDQ443 (Drug)
Arm D
JDQ443 in combination with TNO155 and tislelizumab
干预措施: TNO155 (Drug)
Arm D
JDQ443 in combination with TNO155 and tislelizumab
干预措施: tislelizumab (Biological)
结局指标
主要结局
Dose Escalation: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment
时间窗: 21 days
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as having a suspected relationship to study drug, and unrelated to disease, disease progression, inter-current illness, or concomitant medications that occurs within the first cycle of treatment
Dose Escalation: Incidence and severity of adverse events (AEs) and serious adverse events (SAEs)
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).
Dose Escalation: Frequency of dose interruptions and reductions, by treatment
时间窗: 24 months
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions.
Dose expansion: frequency of dose interruptions and reductions, by treatment
时间窗: 24 months
Tolerability of study drug will be assessed by summarizing the number of and reason for dose delays and dose reductions. Applies to JDQ443 dose randomization group only.
Dose Expansion: Overall response rate (ORR) per RECIST v1.1, by treatment
时间窗: 24 months
Overall response rate is defined as the proportion of patients with a BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to all groups except the brain metastasis group.
Dose expansion: Overall intracranial response rate (OIRR) per mRANO-BM
时间窗: 24 months
OIRR per mRANO-BM is defined as the proportion of participants with a best overall intracranial response (BOIR) of CR or PR according to mRANO-BM criteria, and will be summarized along with the corresponding 90% and 95% exact CI. Applies to brain metastasis group only.
Dose expansion: ORR per RECIST 1.1 of JDQ443 single agent in patients with non-small cell lung cancer (JDQ443 dose randomization group only)
时间窗: 24 months
Overall response rate is defined as the proportion of patients with BOR of CR or PR according to RECIST 1.1, and will be summarized along with the corresponding 95% exact binomial confidence interval (CI). Applies to JDQ443 dose randomization group only
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 treatment.
Dose expansion: Incidence and severity of AEs and SAEs
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). Applies to JDQ443 dose randomization group only.
Dose expansion: 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 treatment. Applies to JDQ443 dose randomization group only
次要结局
- Dose Escalation and Expansion: Plasma or serum concentration vs time profiles (AUC) by treatment(Up to 24 months)
- Dose Escalation and Expansion: Antidrug antibody (ADA) incidence by treatment(Up to 24 months)
- Dose Expansion: Dose intensity by treatment(24 months)
- Dose Expansion: Incidence and severity of AEs and SAEs by treatment(24 months)
- Dose expansion: Intracranial disease control rate (IDCR) per mRANO-BM(24 months)
- Dose expansion: Best overall intracranial response (BOIR) per mRANO-BM(24 months)
- Dose expansion: Intracranial progression free survival (IPFS) per mRANO-BM(24 months)
- Dose expansion: Duration of intracranial response (DOIR) per mRANO-BM(24 months)
- Dose Escalation and Expansion: ORR per RECIST v1.1(24 months)
- Dose Escalation and Expansion: Best Overall Response (BOR) per RECIST v1.1(24 months)
- Dose Escalation and Expansion: Progression-free survival (PFS) per RECIST v1.1, Overall Survival (OS)(24 months)
- Dose Escalation and Expansion: Duration of Response (DOR) per RECIST v1.1(24 months)
- Dose Escalation and Expansion: Disease Control Rate (DCR) per RECIST v1.1(24 months)
- Dose Escalation and Expansion: Plasma concentration (Cmax) by treatment(Up to 24 months)
- Dose Escalation and Expansion: Time to achieve Cmax (Tmax) by treatment(Up to 24 months)
- Dose Expansion: Frequency of dose interruptions and reductions, by treatment(24 months)
- Dose Expansion: Incidence and severity of dose limiting toxicities (DLTs) during the first cycle of monotherapy or combination treatment(21 days)