Clinical trial NCT04165031: A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation
Official title: A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
PHASE2
Conditions: Advanced Solid Tumor
Non-Small Cell Lung Cancer
Colorectal Cancer
Lead sponsor: Eli Lilly and Company
Sponsor class: INDUSTRY
First posted: 2019-11-15
Enrollment: 5
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The reason for this study is to see if the study drug LY3499446 is safe and effective in participants with solid tumors with KRAS G12C mutation.


Eligibility criteria: Inclusion Criteria:

* Participants must have diagnosis of a solid tumor with KRAS G12C mutation that did not respond to at least 1 line of standard therapy and has spread to other part(s) of the body
* For phase II, participants must be willing to have new tumor tissue biopsies (doctor removes a small amount of tissue) during the study if it does not cause undue risks to health
* Participants must be willing to use highly effective birth control
* Participants must have adequate organ function
* Participants must be able to swallow capsules

Exclusion Criteria:

* Participants must not have certain infections such as hepatitis or tuberculosis or HIV that is not well controlled
* Participants must not have another serious medical condition including a serious heart condition, such as congestive heart failure, unstable angina pectoris, or heart attack within the last three months
* Participants must not have cancer of the central nervous system that is not stable
* Participants must not be pregnant or breastfeeding
* Participants must not use herbal supplements

Primary outcomes:
measure: Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
timeFrame: Cycle 1 (21 Day Cycle)
measure: Phase 2: Overall Response Rate (ORR): Percentage of Participants Who Achieve Complete Response (CR) or Partial Response (PR) in Colorectal Cancer (CRC) Cohorts and Other Tumors Cohort
timeFrame: Baseline through Measured Progressive Disease
measure: Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)
timeFrame: Baseline to Objective Progression or Death Due to Any Cause
Secondary outcomes:
measure: Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446
timeFrame: Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
measure: Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib
timeFrame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
measure: Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab
timeFrame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
measure: Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib
timeFrame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
measure: Phase 1: ORR: Percentage of Participants Who Achieve CR or PR
timeFrame: Baseline through Measured Progressive Disease (Up to 11 Months)
measure: Phase 1: PFS
timeFrame: Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)
measure: Phase 1: Duration of Response (DoR)
timeFrame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
measure: Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD
timeFrame: Baseline through Measured Progressive Disease (Up to 11 Months)
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana Univ Melvin & Bren Simon Cancer Center
state: Indiana
city: Middletown
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New Jersey
city: Harrison
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Darlinghurst
country: Australia
facility: St Vincent's Hospital
state: New South Wales
city: Nedlands
country: Australia
facility: Linear Clinical Research Ltd
state: Western Australia
Study officials:
affiliation: Eli Lilly and Company
name: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST)
role: STUDY_DIRECTOR
References: