A Phase 1a/1b Trial of LY3962673 in Participants With KRAS G12D-Mutant Solid Tumors
Trial Snapshot
- Phase
- Phase 1
- Status
- Recruiting
- Sponsor
- Eli Lilly and Company
- Enrollment
- 630
- Locations
- 105
- Primary Endpoint
- 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
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts 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.
- •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
- •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.
Arms & Interventions
Phase 1a: LY3962673 Dose Escalation
Escalating doses of LY3962673 administered orally.
Intervention: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: Gemcitabine (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: nab-paclitaxel (Drug)
Experimental: Phase 1a: LY3962673 Monotherapy
LY3962673 administered orally
Intervention: LY3962673 (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: Cetuximab (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: Oxaliplatin (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: leucovorin (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: Irinotecan (Drug)
Phase 1b: LY3962673 Dose Expansion
LY3962673 administered orally either alone or in combination with other chemotherapy agents.
Intervention: 5-fluorouracil (Drug)
Outcomes
Primary Outcomes
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
Time Frame: 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
Time Frame: During the first 28-day cycle of LY3962673 treatment
Phase 1a: Number of Participants with DLT Equivalent Toxicities
Time Frame: During the first 28-day cycle of LY3962673 treatment
Phase 1b: Overall Response Rate (ORR)
Time Frame: 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)
Time Frame: Up to approximately 5 years
BOR per investigator assessed RECIST 1.1
Phase 1b: Duration of Response (DOR)
Time Frame: Up to approximately 5 years
DOR per investigator assessed RECIST 1.1
Phase 1b: Time to Response (TTR)
Time Frame: Up to approximately 5 years
TTR per investigator assessed RECIST 1.1
Phase 1b: Disease Control Rate (DCR)
Time Frame: Up to approximately 5 years
DCR per investigator assessed RECIST 1.1
Secondary Outcomes
- 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)