Study Stopped
The study was terminated due to an unexpected toxicity finding.
A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation
A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation
3 other identifiers
interventional
5
2 countries
6
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1
Started Nov 2019
6 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
November 14, 2019
CompletedFirst Posted
Study publicly available on registry
November 15, 2019
CompletedStudy Start
First participant enrolled
November 28, 2019
CompletedPrimary Completion
Last participant's last visit for primary outcome
October 30, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
October 30, 2020
CompletedResults Posted
Study results publicly available
November 24, 2021
CompletedNovember 24, 2021
October 1, 2021
11 months
November 14, 2019
October 27, 2021
October 27, 2021
Conditions
Outcome Measures
Primary Outcomes (3)
Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
DLT is defined as an event that is clinically significant and not clearly related to disease progression or intercurrent illness that occurred within the DLT observation period of the Cycle 1 timeframe.
Cycle 1 (21 Day Cycle)
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
ORR is defined as percentage of participants who achieved a CR or PR out of all the participants treated. Tumor responses were measured and record using Response Evaluation Criteria in Solid Tumors v1.1 (RECIST) v1.1 guidelines. CR is defined as the disappearance of all targeted and non-target lesions and no appearance of new lesions. PR is defined as at least a 30% decrease in the sum of the longest diameter (LD) of target lesions (taking as reference the baseline sum LD), no progression of non-target lesions and no appearance of new lesions.
Baseline through Measured Progressive Disease
Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)
PFS was defined as the time from study enrollment (for non-randomized cohorts)/ the time from randomization (for randomized cohorts) to the first observation of progressive disease (PD) or death without documented disease progression per RECIST V1.1 criteria.
Baseline to Objective Progression or Death Due to Any Cause
Secondary Outcomes (8)
Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446
Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib
Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab
Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib
Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
Phase 1: ORR: Percentage of Participants Who Achieve CR or PR
Baseline through Measured Progressive Disease (Up to 11 Months)
- +3 more secondary outcomes
Study Arms (6)
LY3499446 Phase 1 Cohort A1 High Dose
EXPERIMENTALParticipants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
LY3499446 Phase 1 Cohort AO Mid Dose
EXPERIMENTALParticipant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
LY3499446 Phase 1 Cohort A-2 Low Dose
EXPERIMENTALParticipants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
LY3499446 + Combination Drugs Phase 1
EXPERIMENTALLY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). This trial was terminated prior to initiation of combination therapy cohorts.
LY3499446 Monotherapy + Combination Drugs Phase 2
EXPERIMENTALLY3499446 as oral monotherapy and LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). The trial was terminated prior to initiation of Phase 2 of this study.
Docetaxel Phase 2
ACTIVE COMPARATORDocetaxel IV infusion. The trial was terminated prior to initiation of Phase 2 of this study.
Interventions
Administered orally
Administered orally
Administered IV
Administered orally
Eligibility Criteria
You may qualify if:
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (6)
Indiana Univ Melvin & Bren Simon Cancer Center
Indianapolis, Indiana, 46202, United States
Memorial Sloan Kettering Cancer Center
Middletown, New Jersey, 07748, United States
Memorial Sloan Kettering Cancer Center
Harrison, New York, 10604, United States
Memorial Sloan Kettering Cancer Center
New York, New York, 10022, United States
St Vincent's Hospital
Darlinghurst, New South Wales, 2010, Australia
Linear Clinical Research Ltd
Nedlands, Western Australia, 6009, Australia
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Limitations and Caveats
The study was terminated due to an unexpected toxicity finding.
Results Point of Contact
- Title
- Chief Medical Officer
- Organization
- Eli Lilly and Company
Study Officials
- STUDY DIRECTOR
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)
Eli Lilly and Company
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- GT60
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
November 14, 2019
First Posted
November 15, 2019
Study Start
November 28, 2019
Primary Completion
October 30, 2020
Study Completion
October 30, 2020
Last Updated
November 24, 2021
Results First Posted
November 24, 2021
Record last verified: 2021-10
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, CSR
- Time Frame
- Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting.
- Access Criteria
- A research proposal must be approved by an independent review panel and researchers must sign a data sharing agreement.
Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement.