A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation
试验速览
- 阶段
- 1 期
- 状态
- 终止
- 入组人数
- 5
- 试验地点
- 4
- 主要终点
- Phase 2: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) in Colorectal Cancer (CRC) Cohorts and Other Tumors Cohort
研究概览
简要总结
The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation.
研究设计
- 研究类型
- Interventional
- 分配方式
- 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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body
- •For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health
- •Participants must be willing to use highly effective birth control
- •Participants must have adequate organ function
- •Participants must be able to swallow capsules
排除标准
- •Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled
- •Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
- •Participants must not have cancer of the central nervous system that is not stable
- •Participants must not be pregnant or breastfeeding
- •Participants must not use herbal supplements
研究组 & 干预措施
LY3499446 Phase 1 Cohort A1 High Dose
Participants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
干预措施: LY3499446 (Drug)
LY3499446 Phase 1 Cohort AO Mid Dose
Participant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
干预措施: LY3499446 (Drug)
LY3499446 Phase 1 Cohort A-2 Low Dose
Participants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
干预措施: LY3499446 (Drug)
LY3499446 + Combination Drugs Phase 1
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
This trial was terminated prior to initiation of combination therapy cohorts.
干预措施: LY3499446 (Drug)
LY3499446 + Combination Drugs Phase 1
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
This trial was terminated prior to initiation of combination therapy cohorts.
干预措施: Abemaciclib (Drug)
LY3499446 + Combination Drugs Phase 1
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
This trial was terminated prior to initiation of combination therapy cohorts.
干预措施: Cetuximab (Drug)
LY3499446 + Combination Drugs Phase 1
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
This trial was terminated prior to initiation of combination therapy cohorts.
干预措施: Erlotinib (Drug)
LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
The trial was terminated prior to initiation of Phase 2 of this study.
干预措施: LY3499446 (Drug)
LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
The trial was terminated prior to initiation of Phase 2 of this study.
干预措施: Abemaciclib (Drug)
LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
The trial was terminated prior to initiation of Phase 2 of this study.
干预措施: Cetuximab (Drug)
LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).
The trial was terminated prior to initiation of Phase 2 of this study.
干预措施: Erlotinib (Drug)
Docetaxel Phase 2
Docetaxel IV infusion.
The trial was terminated prior to initiation of Phase 2 of this study.
干预措施: Docetaxel (Drug)
结局指标
主要结局
Phase 2: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) in Colorectal Cancer (CRC) Cohorts and Other Tumors Cohort
时间窗: Baseline through Measured Progressive Disease
ORR is defined as percentage of participants who achieved a CR or PR out of all the participants treated. Tumor responses were measured and record using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) v1.1 guidelines. CR is defined as the disappearance of all targeted and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.
Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
时间窗: Cycle 1 (21 Day Cycle)
DLT is defined as an event that is clinically significant and not clearly related to disease progression or intercurrent illness that occurred within the DLT observation period of the Cycle 1 timeframe.
Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)
时间窗: Baseline to Objective Progression or Death Due to Any Cause
PFS was defined as the time from study enrollment (for non-randomized cohorts)/ the time from randomization (for randomized cohorts) to the first observation of progressive disease (PD) or death without documented disease progression per RECIST V1.1 criteria.
次要结局
- Phase 1: PFS(Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months))
- Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib(Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles))
- Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446(Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose)
- Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab(Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles))
- Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib(Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles))
- Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD(Baseline through Measured Progressive Disease (Up to 11 Months))
- Phase 1: ORR: Percentage of Participants Who Achieve CR or PR(Baseline through Measured Progressive Disease (Up to 11 Months))
- Phase 1: Duration of Response (DoR)(Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months))