A Phase 1a/1b Trial of LY3962673 in Participants With KRAS G12D-Mutant Solid Tumors
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 630
- 试验地点
- 105
- 主要终点
- 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
研究概览
简要总结
The main purpose of this study is to assess safety & tolerability and antitumor activity of LY3962673 as monotherapy and in combination with other chemotherapy agents in participants with KRAS G12D-mutant advanced solid tumor types. The study is expected to last approximately 5 years.
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
- •Have Histological or cytologically proven diagnosis of locally advanced, unresectable, and/or metastatic cancer and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.
- •Have evidence of KRAS G12D mutation in tumor tissue or circulating tumor DNA
- •Have an ECOG performance status of ≤ 1
- •Must have received ≥ 1 prior line of systemic chemotherapy for advanced or metastatic disease
- •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 National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v5.0 Grade
- •Have significant cardiovascular disease as unstable angina or acute coronary syndrome, history of myocardial infarction, known reduced left ventricular ejection fraction.
- •Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection.
- •Have known active hepatitis B virus (HBV) and hepatitis C virus (HCV).
- •Have other active malignancy unless in remission with life expectancy greater than (>) 2 years.
研究组 & 干预措施
Phase 1a: LY3962673 Dose Escalation
Escalating doses of LY3962673 administered orally.
干预措施: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: Gemcitabine (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: nab-paclitaxel (Drug)
Experimental: Phase 1a: LY3962673 Monotherapy
LY3962673 administered orally
干预措施: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: Cetuximab (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: Oxaliplatin (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: leucovorin (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: Irinotecan (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
干预措施: 5-fluorouracil (Drug)
结局指标
主要结局
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: Baseline through 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.
Phase 1a: Number of Participants with DLT
时间窗: During the first 28-day cycle of LY3962673 treatment
Phase 1a: Number of Participants with DLT Equivalent Toxicities
时间窗: During the first 28-day cycle of LY3962673 treatment
Phase 1b: Overall Response Rate (ORR)
时间窗: Up to approximately 5 years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Phase 1b: Best Overall Response (BOR)
时间窗: Up to approximately 5 years
BOR per investigator assessed RECIST 1.1
Phase 1b: Duration of Response (DOR)
时间窗: Up to approximately 5 years
DOR per investigator assessed RECIST 1.1
Phase 1b: Time to Response (TTR)
时间窗: Up to approximately 5 years
TTR per investigator assessed RECIST 1.1
Phase 1b: Disease Control Rate (DCR)
时间窗: Up to approximately 5 years
DCR per investigator assessed RECIST 1.1
次要结局
- Phase 1a: 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)
- Time to Response (TTR)(Up to approximately 5 years)
- Disease Control Rate (DCR)(Up to approximately 5 years)
- Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3962673(Predose through Day 168)
- PK: Time to Maximum Concentration (Tmax) of LY3962673(Predose through Day 168)
- PK: Area Under the Concentration Versus Time Curve (AUC) of LY3962673(Predose through Day 168)