- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04165031
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
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
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New South Wales
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Darlinghurst, New South Wales, Australia, 2010
- St Vincent's Hospital
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Western Australia
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Nedlands, Western Australia, Australia, 6009
- Linear Clinical Research Ltd
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Indiana
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Indianapolis, Indiana, United States, 46202
- Indiana Univ Melvin & Bren Simon Cancer Center
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New Jersey
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Middletown, New Jersey, United States, 07748
- Memorial Sloan Kettering Cancer Center
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New York
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Harrison, New York, United States, 10604
- Memorial Sloan Kettering Cancer Center
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New York, New York, United States, 10022
- Memorial Sloan Kettering Cancer Center
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: LY3499446 Phase 1 Cohort A1 High Dose
Participants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
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Administered orally
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Experimental: LY3499446 Phase 1 Cohort AO Mid Dose
Participant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
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Administered orally
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Experimental: LY3499446 Phase 1 Cohort A-2 Low Dose
Participants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
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Administered orally
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Experimental: LY3499446 + Combination Drugs Phase 1
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). This trial was terminated prior to initiation of combination therapy cohorts. |
Administered orally
Other Names:
Administered orally
Administered IV
Administered orally
|
Experimental: LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 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. |
Administered orally
Other Names:
Administered orally
Administered IV
Administered orally
|
Active Comparator: Docetaxel Phase 2
Docetaxel IV infusion. The trial was terminated prior to initiation of Phase 2 of this study. |
Administered IV
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
Time Frame: Cycle 1 (21 Day Cycle)
|
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.
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Cycle 1 (21 Day Cycle)
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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
Time Frame: Baseline through Measured Progressive Disease
|
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.
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Baseline through Measured Progressive Disease
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Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)
Time Frame: Baseline to Objective Progression or Death Due to Any Cause
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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.
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Baseline to Objective Progression or Death Due to Any Cause
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446
Time Frame: Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
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Average concentration after the first dose of LY3499446.
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Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
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Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib
Time Frame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib
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Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab
Time Frame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab
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Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib
Time Frame: Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib
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Predose Cycle 1 Day 1 through Cycle 3 Day 1 (21 Day Cycles)
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Phase 1: ORR: Percentage of Participants Who Achieve CR or PR
Time Frame: Baseline through Measured Progressive Disease (Up to 11 Months)
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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.
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Baseline through Measured Progressive Disease (Up to 11 Months)
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Phase 1: PFS
Time Frame: Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)
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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) overall response or death without documented disease progression per RECIST V1.1 criteria.
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Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)
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Phase 1: Duration of Response (DoR)
Time Frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
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DoR was defined as the time from the date measurement criteria for CR or PR (whichever is first recorded) are first met until the first date that disease is recurrent or objective progression is observed, per RECIST v1.1 criteria, or the date of death from any cause in the absence of objectively determined disease progression or recurrence.
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Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
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Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD
Time Frame: Baseline through Measured Progressive Disease (Up to 11 Months)
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DCR was defined as the percentage of participants who achieved a best overall response (BOR) of confirmed CR, confirmed PR, or SD out of all participants treatment.
Best response is determined from a sequence of responses assessed.
Two determinations of PR or better before progression, but not qualifying for a CR, are required for a best response of PR.
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.
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Baseline through Measured Progressive Disease (Up to 11 Months)
|
Collaborators and Investigators
Sponsor
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Respiratory Tract Diseases
- Neoplasms
- Lung Diseases
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Respiratory Tract Neoplasms
- Thoracic Neoplasms
- Carcinoma, Bronchogenic
- Bronchial Neoplasms
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Lung Neoplasms
- Carcinoma, Non-Small-Cell Lung
- Colorectal Neoplasms
- Molecular Mechanisms of Pharmacological Action
- Enzyme Inhibitors
- Antineoplastic Agents
- Tubulin Modulators
- Antimitotic Agents
- Mitosis Modulators
- Antineoplastic Agents, Immunological
- Protein Kinase Inhibitors
- Docetaxel
- Erlotinib Hydrochloride
- Cetuximab
Other Study ID Numbers
- 17501 (Other Identifier: City of Hope Comprehensive Cancer Center)
- J2K-MC-JZKA (Other Identifier: Eli Lilly and Company)
- 2019-003070-53 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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