A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation

Colorectal Cancer Clinical Trial

Official title:

A Phase 1/2 Study of LY3499446 Administered to Patients With Advanced Solid Tumors With KRAS G12C Mutation

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT04165031
• Other study ID #: 17501
• Secondary ID: J2K-MC-JZKA2019-
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: November 28, 2019
• Est. completion date: October 30, 2020

Study information

• Verified date: October 2021
• Source: Eli Lilly and Company
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 5
• Est. completion date: October 30, 2020
• Est. primary completion date: October 30, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Advanced Solid Tumor
• Carcinoma, Non-Small-Cell Lung
• Colorectal Cancer
• Colorectal Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Drug:
• LY3499446
Administered orally
• Abemaciclib
Administered orally
• Cetuximab
Administered IV
• Erlotinib
Administered orally
• Docetaxel
Administered IV

Locations

Country	Name	City	State
Australia	St Vincent's Hospital	Darlinghurst	New South Wales
Australia	Linear Clinical Research Ltd	Nedlands	Western Australia
United States	Memorial Sloan Kettering Cancer Center	Harrison	New York
United States	Indiana Univ Melvin & Bren Simon Cancer Center	Indianapolis	Indiana
United States	Memorial Sloan Kettering Cancer Center	Middletown	New Jersey
United States	Memorial Sloan Kettering Cancer Center	New York	New York

Sponsors (1)

Lead Sponsor	Collaborator
Eli Lilly and Company

Countries where clinical trial is conducted

United States,  Australia, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)
Primary	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
Primary	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	Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446	Average concentration after the first dose of LY3499446.	Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose
Secondary	Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib	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)
Secondary	Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab	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)
Secondary	Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib	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)
Secondary	Phase 1: ORR: Percentage of Participants Who Achieve CR or PR	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 (Up to 11 Months)
Secondary	Phase 1: PFS	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.	Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)
Secondary	Phase 1: Duration of Response (DoR)	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.	Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)
Secondary	Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD	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.	Baseline through Measured Progressive Disease (Up to 11 Months)

External Links

•   A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation