A Phase 1/2 interventional study of LY3499446 and Abemaciclib in Advanced Solid Tumor, Non-Small Cell Lung Cancer and Colorectal Cancer, sponsored by Eli Lilly and Company. Terminated at 6 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2021-11-24.
Sponsored by Eli Lilly and Company · Phase 1/2, Interventional, and Treatment
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.
6,488 studies on the registry are indexed under Carcinoma, Non-Small-Cell Lung; 1,632 are open to participants now.
This study's enrollment of 5 is below the median of 62 across 5,213 interventional studies indexed under Carcinoma, Non-Small-Cell Lung.
Browse Carcinoma, Non-Small-Cell Lung studies →Eli Lilly and Company is the lead sponsor of 2,048 studies on the registry; 140 are open to participants now.
Of its 521 completed or terminated interventional studies of FDA-regulated products, 341 (65%) have results posted.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Participants received high dose LY3499446 as oral monotherapy twice daily (BID) in 21-day cycles.
Drug: LY3499446
Participant received mid dose LY3499446 as oral monotherapy once every other day (QOD) in 21-day cycles.
Drug: LY3499446
Participants received low dose LY3499446 as oral monotherapy once daily (QD) in 21-Day cycles.
Drug: LY3499446
LY3499446 combined with either abemaciclib (orally), erlotinib (orally), or cetuximab (IV). This trial was terminated prior to initiation of combination therapy cohorts.
Drug: LY3499446 · Drug: Abemaciclib · Drug: Cetuximab · Drug: Erlotinib
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.
Drug: LY3499446 · Drug: Abemaciclib · Drug: Cetuximab · Drug: Erlotinib
Docetaxel IV infusion. The trial was terminated prior to initiation of Phase 2 of this study.
Drug: Docetaxel
Administered orally
Administered orally
Also known as: LY2835219
Administered IV
Administered orally
Administered IV
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
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
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
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 (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)
| Milestone | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 |
|---|---|---|---|---|---|---|
| Started | 2 | 1 | 2 | 0 | 0 | 0 |
| Received at least one dose of study drug | 2 | 1 | 2 | 0 | 0 | 0 |
| Completed | 1 | 0 | 1 | 0 | 0 | 0 |
| Not completed | 1 | 1 | 1 | 0 | 0 | 0 |
| Withdrew: Adverse event | 1 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Withdrawal by subject | 0 | 0 | 1 | 0 | 0 | 0 |
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.
| Participants | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) |
|---|---|---|---|
| Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs) | 2 | 1 | 1 |
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Average concentration after the first dose of LY3499446.
| nanograms per milliliter (ng/mL) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) |
|---|---|---|---|
| Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446 | NA ± NA | NA ± NA | NA ± NA |
PK: Average Concentration at Steady State of LY3499446 in Combination with Abemaciclib
No measurements were reported for this outcome.
PK: Average Concentration at Steady State of LY3499446 in Combination with Cetuximab
No measurements were reported for this outcome.
PK: Average Concentration at Steady State of LY3499446 in Combination with Erlotinib
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
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.
No measurements were reported for this outcome.
Collected over Baseline up to 11 months. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| LY3499446 Phase 1 Cohort A1 (High Dose) | 1/2 (50%) | 0/2 (0%) | 2/2 (100%) |
| LY3499446 Phase 1 Cohort AO (Mid Dose) | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| LY3499446 Phase 1 Cohort A-2 (Low Dose) | 1/2 (50%) | 1/2 (50%) | 2/2 (100%) |
| Event | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) |
|---|---|---|---|
| PyrexiaGeneral disorders | 0/2 | 0/1 | 1/2 |
| DyspnoeaRespiratory, thoracic and mediastinal disorders | 0/2 | 0/1 | 1/2 |
| HypoxiaRespiratory, thoracic and mediastinal disorders | 0/2 | 0/1 | 1/2 |
| Pleural effusionRespiratory, thoracic and mediastinal disorders | 0/2 | 0/1 | 1/2 |
| Respiratory failureRespiratory, thoracic and mediastinal disorders | 0/2 | 0/1 | 1/2 |
| Event | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) |
|---|---|---|---|
| AnaemiaBlood and lymphatic system disorders | 0/2 | 1/1 | 0/2 |
| HaemolysisBlood and lymphatic system disorders | 2/2 | 1/1 | 1/2 |
| NauseaGastrointestinal disorders | 0/2 | 0/1 | 2/2 |
| FatigueGeneral disorders | 0/2 | 0/1 | 2/2 |
| Blood bilirubin increasedInvestigations | 2/2 | 1/1 | 0/2 |
| LeukocytosisBlood and lymphatic system disorders | 0/2 | 0/1 | 1/2 |
| Cardiac arrestCardiac disorders | 0/2 | 0/1 | 1/2 |
| PalpitationsCardiac disorders | 0/2 | 0/1 | 1/2 |
| ConstipationGastrointestinal disorders | 0/2 | 0/1 | 1/2 |
| Urinary tract infectionInfections and infestations | 0/2 | 0/1 | 1/2 |
All participants who received at least one dose of study drug
| Age, Categorical(Participants) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| <=18 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Between 18 and 65 years | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| >=65 years | 1 | 1 | 2 | 0 | 0 | 0 | 4 |
| Sex: Female, Male(Participants) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| Female | 1 | 1 | 2 | 0 | 0 | 0 | 4 |
| Male | 1 | 0 | 0 | 0 | 0 | 0 | 1 |
| Ethnicity (NIH/OMB)(Participants) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Not Hispanic or Latino | 2 | 1 | 2 | 0 | 0 | 0 | 5 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| White | 2 | 1 | 2 | 0 | 0 | 0 | 5 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Region of Enrollment(Participants) | LY3499446 Phase 1 Cohort A1 (High Dose) | LY3499446 Phase 1 Cohort AO (Mid Dose) | LY3499446 Phase 1 Cohort A-2 (Low Dose) | LY3499446 + Combination Drug Phase 1 | LY3499446 Monotherapy + Combination Drug Phase 2 | Docetaxel Phase 2 | Total |
|---|---|---|---|---|---|---|---|
| United States | 0 | 1 | 2 | 0 | 0 | 0 | 3 |
| Australia | 2 | 0 | 0 | 0 | 0 | 0 | 2 |
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — 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.
Supporting information: Study protocol, Sap, Csr
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Carcinoma, Non-Small-Cell Lung→
Eli Lilly and Company