A Phase 1a/1b Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 进行中（未招募）
- 入组人数
- 750
- 试验地点
- 47
- 主要终点
- Number of Participants with Dose-limiting Toxicities (DLTs)
研究概览
简要总结
The main purpose of the study is to assess whether the study drug, LY4066434, is safe and tolerable when administered to participants with locally advanced or metastatic solid tumors with certain KRAS mutations. LY4066434 will be given alone or in combination with other treatments. The study will have 2 parts: monotherapy dose escalation and dose optimization. The study is expected to last up to approximately 5 years.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non 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 65+ years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Have evidence of KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor DNA
- •Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer
- •Have measurable disease per RECIST 1.1
- •Have an ECOG performance status of ≤1
- •Must not be pregnant and/or planning to breastfeed during the trial or within 180 days of the last dose of trial intervention
- •Must be able to swallow tablets
- •Participants with asymptomatic or treated CNS disease may be eligible
排除标准
- •Have known active CNS metastases and/or carcinomatous meningitis
- •Have any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 1 at the time of starting trial treatment, except for alopecia, hearing loss, peripheral neuropathy and ongoing endocrinopathies controlled on appropriate replacement therapy
- •Have significant cardiovascular disease defined as unstable angina or acute coronary syndrome, history of myocardial infarction, known left ventricular ejection fraction or heart failure, uncontrolled or symptomatic arrhythmias.
- •Have known active hepatitis B virus (HBV), hepatitis C virus (HCV) or untreated HIV infection
- •Have other active malignancy unless in remission with life expectancy greater than 2 years.
- •Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection
- •Have history of non-infectious pneumonitis/interstitial lung disease that received steroids or has current clinically significant pneumonitis/interstitial lung disease
研究组 & 干预措施
LY4066434 Monotherapy Dose Escalation
Escalating doses of LY4066434 administered orally.
干预措施: LY4066434. (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: LY4066434. (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Cetuximab (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Oxaliplatin (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Leucovorin (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Nab paclitaxel (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Gemcitabine (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Irinotecan (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: 5Fluorouracil (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Carboplatin (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Cisplatin (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Pemetrexed (Drug)
LY4066434 Dose Optimization
LY4066434 administered orally either alone or with another investigational agent.
干预措施: Pembrolizumab (Drug)
结局指标
主要结局
Number of Participants with Dose-limiting Toxicities (DLTs)
时间窗: During the first cycle of LY4066434 treatment (up to 28 days)
Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
时间窗: Up to approximately 5 years
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.
次要结局
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone(Predose through Day 168)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents(Predose through Day 168)
- PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone(Predose through Day 168)
- Overall Response Rate (ORR)(Up to approximately 5 years)
- Best Overall Response (BOR)(Up to approximately 5 years)
- Duration of Response (DOR)(Up to approximately 5 years)
- Disease Control Rate (DCR)(Up to approximately 5 years)
- Time to Response (TTR)(Up to approximately 5 years)
- PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents(Predose through Day 168)
- PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone(Predose through Day 168)
- PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents(Predose through Day 168)