A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors
- Conditions
- Interventions
- Registration Number
- NCT06607185
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
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 optimizatio...
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 750
- 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
- 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, 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) and 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description LY4066434 Monotherapy Dose Escalation LY4066434. Escalating doses of LY4066434 administered orally. LY4066434 Dose Optimization LY4066434. LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Cetuximab LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Nab paclitaxel LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Gemcitabine LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Oxaliplatin LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Leucovorin LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Irinotecan LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization 5Fluorouracil LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Carboplatin LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Cisplatin LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Pemetrexed LY4066434 administered orally either alone or with another investigational agent. LY4066434 Dose Optimization Pembrolizumab LY4066434 administered orally either alone or with another investigational agent.
- Primary Outcome Measures
Name Time Method Number of Participants with Dose-limiting Toxicities (DLTs) 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 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.
- Secondary Outcome Measures
Name Time Method PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone Predose through Day 168 PK: AUC of LY4066434
PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents Predose through Day 168 PK: AUC of LY4066434
PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents Predose through Day 168 PK: Tmax of LY4066434
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone Predose through Day 168 PK: Cmax of LY4066434
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents Predose through Day 168 PK: Cmax of LY4066434
Time to Response (TTR) Up to approximately 5 years TTR as assessed by investigator per RECIST v1.1
PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone Predose through Day 168 PK: Tmax of LY4066434
Duration of Response (DOR) Up to approximately 5 years DOR as assessed by investigator per RECIST v1.1
Disease Control Rate (DCR) Up to approximately 5 years DCR as assessed by investigator per RECIST v1.1
Overall Response Rate (ORR) Up to approximately 5 years ORR as assessed by investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Best Overall Response (BOR) Up to approximately 5 years BOR as assessed by investigator per RECIST v1.1
Trial Locations
- Locations (24)
Hsin-Chu Hospital
🇨🇳Hsin-chu, Taiwan
National Taiwan University Hospital
🇨🇳Taipei, Taiwan
START Midwest
🇺🇸Grand Rapids, Michigan, United States
City of Hope National Medical Center
🇺🇸Duarte, California, United States
UCLA
🇺🇸Santa Monica, California, United States
University of Alabama Birmingham
🇺🇸Birmingham, Alabama, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana-Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
Memorial Sloan Kettering
🇺🇸New York, New York, United States
Columbia University
🇺🇸New York, New York, United States
Cleveland Clinic
🇺🇸Cleveland, Ohio, United States
University of Pittsburgh Medical Center
🇺🇸Pittsburgh, Pennsylvania, United States
SCRI Oncology Partners
🇺🇸Nashville, Tennessee, United States
University of Texas Southwestern Medical Center at Dallas
🇺🇸Dallas, Texas, United States
MD Anderson
🇺🇸Houston, Texas, United States
South Texas Accelerated Research Therapeutics (START)
🇺🇸San Antonio, Texas, United States
USO-Virginia Cancer Specialists, PC
🇺🇸Fairfax, Virginia, United States
Cliniques universitaires Saint-Luc
🇧🇪Bruxelles, Brussel, Belgium
Institut Jules Bordet
🇧🇪Brussel - Capital, Belgium
National Cancer Center Hospital East
🇯🇵Kashiwa, Chiba, Japan
Tominaga Hospital
🇯🇵Sunto-Gun, Shizuoka, Japan
National Cancer Center Hospital
🇯🇵Chuo-ku, Tokyo, Japan
The Cancer Institute Hospital of JFCR
🇯🇵Koto City, Tokyo, Japan
Hospital Universitari Vall d'Hebron
🇪🇸Barcelona, Spain