Colorectal Cancer, Non-small Cell Lung Cancer, Pancreatic Ductal Adenocarcinoma
Conditions
Keywords
KRAS G12D, KRAS, LY3962673, Cetuximab, nab-paclitaxel, Gemcitabine, Oxaliplatin, Leucovorin, Irinotecan, 5-fluorouracil
Brief summary
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.
Interventions
DRUGLY3962673
Administered orally.
DRUGCetuximab
Administered intravenously.
DRUGGemcitabine
Administered intravenously.
DRUGnab-paclitaxel
Administered intravenously.
DRUGOxaliplatin
Administered intravenously.
DRUGleucovorin
Administered intravenously.
DRUGIrinotecan
Administered intravenously.
DRUG5-fluorouracil
Administered intravenously.
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Phase 1a/1b
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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 1.1. * 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.
Exclusion criteria
* 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 1. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 | 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 | During the first 28-day cycle of LY3962673 treatment | — |
| Phase 1a: Number of Participants with DLT Equivalent Toxicities | During the first 28-day cycle of LY3962673 treatment | — |
| Phase 1b: Overall Response Rate (ORR) | 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) | Up to approximately 5 years | BOR per investigator assessed RECIST 1.1 |
| Phase 1b: Duration of Response (DOR) | Up to approximately 5 years | DOR per investigator assessed RECIST 1.1 |
| Phase 1b: Time to Response (TTR) | Up to approximately 5 years | TTR per investigator assessed RECIST 1.1 |
| Phase 1b: Disease Control Rate (DCR) | Up to approximately 5 years | DCR per investigator assessed RECIST 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Phase 1a: Overall Response Rate (ORR) | Up to approximately 5 years | ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1) |
| Best Overall Response (BOR) | Up to approximately 5 years | BOR per investigator assessed RECIST 1.1 |
| Duration of Response (DOR) | Up to approximately 5 years | DOR per investigator assessed RECIST 1.1 |
| Time to Response (TTR) | Up to approximately 5 years | TTR per investigator assessed RECIST 1.1 |
| Disease Control Rate (DCR) | Up to approximately 5 years | DCR per investigator assessed RECIST 1.1 |
| Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY3962673 | Predose through Day 168 | PK: Cmax of LY3962673 |
| PK: Time to Maximum Concentration (Tmax) of LY3962673 | Predose through Day 168 | PK: Tmax of LY3962673 |
| PK: Area Under the Concentration Versus Time Curve (AUC) of LY3962673 | Predose through Day 168 | PK: AUC of LY3962673 |
Countries
Canada, China, France, Germany, Ireland, Italy, Japan, Spain, United States
Contacts
CONTACTTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
CONTACTPhysicians interested in becoming principal investigators please contact
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