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

Phase 2TerminatedNCT04165031

Eli Lilly and Company5 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Advanced Solid Tumor Non-Small Cell Lung Cancer Colorectal Cancer

Interventions

LY3499446DRUG

Administered orally

AbemaciclibDRUG

Administered orally

CetuximabDRUG

Administered IV

Erlotinib

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (6)

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

Harrison, New York, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Outcomes

Primary Outcomes

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.

Time frame: 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.

Time frame: 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.

Time frame: Baseline to Objective Progression or Death Due to Any Cause

Secondary Outcomes

Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446

Average concentration after the first dose of LY3499446.

Time frame: 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

Data from ClinicalTrials.gov

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DocetaxelDRUG

Administered IV

St Vincent's Hospital

Darlinghurst, New South Wales, Australia

Linear Clinical Research Ltd

Nedlands, Western Australia, Australia

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)

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

Time frame: 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

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)

Phase 1: ORR: Percentage of Participants Who Achieve CR or PR

Time frame: Baseline through Measured Progressive Disease (Up to 11 Months)

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.

Time frame: Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)

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.

Time frame: Date of CR or PR to Date of Disease Progression or Death Due to Any Cause (Up to 11 Months)

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.

Time frame: Baseline through Measured Progressive Disease (Up to 11 Months)