Advanced Solid Tumor, Colorectal Cancer, Metastatic Solid Tumor, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
KRAS, KRAS mutation, KRASG12C, KRASG12D, KRASG12V, KRASG12S, KRASG12A, KRASG13D, LY4066434, Targeted therapy, Lung cancer, Pancreas cancer, Colon cancer, Rectal cancer, Colorectal cancer, Ovarian cancer, Endometrial cancer, Cholangiocarcinoma, Esophageal cancer, KRAS-mutant tumor, PanKRAS, Pan KRAS
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 optimization. The study is expected to last up to approximately 5 years.
Interventions
DRUGLY4066434.
Administered orally.
DRUGCetuximab
Administered intravenously.
DRUGNab paclitaxel
Administered intravenously.
DRUGGemcitabine
Administered intravenously.
DRUGOxaliplatin
Administered intravenously.
DRUGLeucovorin
Administered intravenously.
DRUGIrinotecan
Administered intravenously.
DRUG5Fluorouracil
Administered intravenously.
DRUGCarboplatin
Administered intravenously.
DRUGCisplatin
Administered intravenously.
DRUGPemetrexed
Administered intravenously.
DRUGPembrolizumab
Administered intravenously.
Sponsors
Eli Lilly and Company
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| Time to Response (TTR) | Up to approximately 5 years | TTR as assessed by investigator per RECIST v1.1 |
| 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 |
| PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone | Predose through Day 168 | PK: Tmax of LY4066434 |
| PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents | Predose through Day 168 | PK: Tmax of LY4066434 |
| 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 |
Countries
Belgium, France, Germany, Italy, Japan, Spain, Taiwan, United States
Contacts
STUDY_DIRECTORCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST)
Eli Lilly and Company
Outcome results
None listed