NCT04165031 · REGISTRY CONDITION SEARCH

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

Found through the registry condition index, not selected as a treatment recommendation. This discovery collection was restricted to studies with posted results.

Phase: PHASE1, PHASE2
Status at capture: TERMINATED
Registry last update: 2021-11-24

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.

Open the original ClinicalTrials.gov record → · Download preserved record

What did the study report?

Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.

flow

Participant flow

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baseline

Baseline characteristics

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outcome · POSTED

Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)

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outcome · POSTED

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

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outcome · POSTED

Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)

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outcome · POSTED

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

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outcome · POSTED

Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Abemaciclib

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outcome · POSTED

Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Cetuximab

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outcome · POSTED

Phase 1: PK: Average Concentration at Steady State of LY3499446 in Combination With Erlotinib

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outcome · POSTED

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

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outcome · POSTED

Phase 1: PFS

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outcome · POSTED

Phase 1: Duration of Response (DoR)

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outcome · POSTED

Phase 1: Disease Control Rate (DCR): Percentage of Participants With a Best Overall Response of CR, PR, and SD

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adverse events

Adverse events

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more info

Limitations, agreements, and source contact

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Who could take part

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
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
Participants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
intervention Names
Drug: LY3499446
label
LY3499446 Phase 1 Cohort A1 High Dose
type
EXPERIMENTAL
description
Participant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
intervention Names
Drug: LY3499446
label
LY3499446 Phase 1 Cohort AO Mid Dose
type
EXPERIMENTAL
description
Participants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
intervention Names
Drug: LY3499446
label
LY3499446 Phase 1 Cohort A-2 Low Dose
type
EXPERIMENTAL
description
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). This trial was terminated prior to initiation of combination therapy cohorts.
intervention Names
Drug: LY3499446
Drug: Abemaciclib
Drug: Cetuximab
Drug: Erlotinib
label
LY3499446 + Combination Drugs Phase 1
type
EXPERIMENTAL
description
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.
intervention Names
Drug: LY3499446
Drug: Abemaciclib
Drug: Cetuximab
Drug: Erlotinib
label
LY3499446 Monotherapy + Combination Drugs Phase 2
type
EXPERIMENTAL
description
Docetaxel IV infusion. The trial was terminated prior to initiation of Phase 2 of this study.
intervention Names
Drug: Docetaxel
label
Docetaxel Phase 2
type
ACTIVE_COMPARATOR

interventions

arm Group Labels
LY3499446 + Combination Drugs Phase 1
LY3499446 Monotherapy + Combination Drugs Phase 2
LY3499446 Phase 1 Cohort A-2 Low Dose
LY3499446 Phase 1 Cohort A1 High Dose
LY3499446 Phase 1 Cohort AO Mid Dose
description
Administered orally
name
LY3499446
type
DRUG
arm Group Labels
LY3499446 + Combination Drugs Phase 1
LY3499446 Monotherapy + Combination Drugs Phase 2
description
Administered orally
name
Abemaciclib
other Names
LY2835219
type
DRUG
arm Group Labels
LY3499446 + Combination Drugs Phase 1
LY3499446 Monotherapy + Combination Drugs Phase 2
description
Administered IV
name
Cetuximab
type
DRUG
arm Group Labels
LY3499446 + Combination Drugs Phase 1
LY3499446 Monotherapy + Combination Drugs Phase 2
description
Administered orally
name
Erlotinib
type
DRUG
arm Group Labels
Docetaxel Phase 2
description
Administered IV
name
Docetaxel
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: NONE

primary Purpose

TREATMENT

Enrollment

count: 5
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
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.
measure
Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs)
time Frame
Cycle 1 (21 Day Cycle)
description
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.
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
time Frame
Baseline through Measured Progressive Disease
description
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.
measure
Phase 2: Progression-Free Survival (PFS) Non-Small Lung Cancer (NSCLC Cohorts)
time Frame
Baseline to Objective Progression or Death Due to Any Cause

secondary Outcomes

description
Average concentration after the first dose of LY3499446.
measure
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
description
PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib
measure
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)
description
PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab
measure
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)
description
PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib
measure
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)
description
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.
measure
Phase 1: ORR: Percentage of Participants Who Achieve CR or PR
time Frame
Baseline through Measured Progressive Disease (Up to 11 Months)
description
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.
measure
Phase 1: PFS
time Frame
Baseline to Objective Progression or Death Due to Any Cause (Up to 11 Months)
description
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.
measure
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)
description
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.
measure
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)

Full study description

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.

Source references