Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Digestive System Diseases

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Colorectal Neoplasms

Carcinoma, Bronchogenic

Bronchial Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Intestinal Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Colonic Diseases

Intestinal Diseases

Rectal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Docetaxel

Cetuximab

Erlotinib Hydrochloride

Tubulin Modulators

Antimitotic Agents

Antineoplastic Agents, Immunological

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Participants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.

Participant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.

Participants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.

LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).

This trial was terminated prior to initiation of combination therapy cohorts.

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.

Docetaxel IV infusion.

The trial was terminated prior to initiation of Phase 2 of this study.

LY3499446

Abemaciclib

Erlotinib

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)

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.

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

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.

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.

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.

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.

Average concentration after the first dose of LY3499446.

PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib

PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab

PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib

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.

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.

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.

Eli Lilly and Company

All participants who received at least one dose of study drug.

LY3499446 Phase 1 Cohort A1 (High Dose)

LY3499446 Phase 1 Cohort AO (Mid Dose)

Participants received low dose LY3499446 as monotherapy orally once QD in 21-day cycles.

LY3499446 Phase 1 Cohort A-2 (Low Dose)

Participants received high dose LY3499446 as oral monotherapy BID in 21-day cycles.

Participant received mid dose LY3499446 as oral monotherapy once QOD in 21-day cycles.

Participants received low dose LY 3499446 as oral monotherapy once QD in 21-day cycles.

LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).

The trial was terminated prior to initiation of this portion.

LY3499446 + Combination Drug Phase 1

LY3499446 monotherapy orally. LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).

The trial was terminated prior to initiation of this portion.

LY3499446 Monotherapy + Combination Drug Phase 2

Docetaxel IV infusion.

The trial was terminated prior to initiation of this portion.

Docetaxel Phase 2

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Australia

Region of Enrollment

All participants who received at least one dose of study drug

The study was terminated due to an unexpected toxicity finding.

Chief Medical Officer

Participants received low dose LY3499446 as oral monotherapy once QD in 21-day cycles.

All participants who received at least one dose of study drug and had a dose limiting toxicity.

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

LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV).

LY3499446 Monotherapy + Combination Drugs Phase 2

Zero participants were analyzed due to early termination of study.

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

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

All participants who have received at least one dose of study drug and had evaluable PK.

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

LY3499446 in combination with abemaciclib orally.

LY3499446 and Abemaciclib Phase 1

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

LY3499446 in combination with cetuximab intravenously (IV).

LY3499446 and Cetuximab Phase 1

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

LY3499446 in combination with erlotinib orally.

LY3499446 Monotherapy and Erlotinib Phase 1

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

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

Participant received mid dose LY3499446 as oral monotherapy QOD in 21-day cycles.

Participants received low dose LY3499446 as oral monotherapy QD in 21-day cycles in 21-day cycles.

Phase 1: PFS

Phase 1: Duration of Response (DoR)

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

Participants received low dose LY 3499446 as oral monotherapy once daily (QD) in 21-day cycles.

Spots Global Cancer Trial Database for A Study of LY3499446 in Participants With Advanced Solid Tumors With KRAS G12C Mutation

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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