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NCT04165031

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

Terminated Phase 1, PHASE2 Results posted Last updated 24 November 2021
What this trial tests

Phase 1, PHASE2 trial testing LY3499446 in Advanced Solid Tumor in 5 participants. Terminated before completion.

Timeline
28 November 2019
Primary endpoint
30 October 2020
30 October 2020

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 1, PHASE2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment5
Start date28 November 2019
Primary completion30 October 2020
Estimated completion30 October 2020
Sites6 locations across United States, Australia

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

18 and older, any sex, with Advanced Solid Tumor or Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Phase 1: Number or Participants With Dose Limiting Toxicities (DLTs) Primary · Cycle 1 (21 Day Cycle)

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.

GroupValue95% CI
LY3499446 Phase 1 Cohort A1 (High Dose)2
LY3499446 Phase 1 Cohort AO (Mid Dose)1
LY3499446 Phase 1 Cohort A-2 (Low Dose)1
Phase 1: Pharmacokinetics (PK): Average Concentration of LY3499446 Secondary · Cycle 1 Day 1: Predose, 0.5, 1, 1.5, 2, 3, 4, 8, 24 hours post-dose

Average concentration after the first dose of LY3499446.

GroupValue95% CI
LY3499446 Phase 1 Cohort A1 (High Dose)NA± NA
LY3499446 Phase 1 Cohort AO (Mid Dose)NA± NA
LY3499446 Phase 1 Cohort A-2 (Low Dose)NA± NA

Adverse events — posted to ClinicalTrials.gov

Time frame: Baseline up to 11 months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

LY3499446 Phase 1 Cohort A1 (High Dose)
Serious: 0/2 (0%)
Deaths: 1/2
LY3499446 Phase 1 Cohort AO (Mid Dose)
Serious: 0/1 (0%)
Deaths: 0/1
LY3499446 Phase 1 Cohort A-2 (Low Dose)
Serious: 1/2 (50%)
Deaths: 1/2

Serious adverse events (5 terms)

ReactionSystemLY3499446 Phase 1 Cohort A…LY3499446 Phase 1 Cohort A…LY3499446 Phase 1 Cohort A…
PyrexiaGeneral disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
HypoxiaRespiratory, thoracic and mediastinal disorders
Pleural effusionRespiratory, thoracic and mediastinal disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Other adverse events (25 terms — click to expand)

ReactionSystemLY3499446 Phase 1 Cohort A…LY3499446 Phase 1 Cohort A…LY3499446 Phase 1 Cohort A…
HaemolysisBlood and lymphatic system disorders
NauseaGastrointestinal disorders
FatigueGeneral disorders
Blood bilirubin increasedInvestigations
AnaemiaBlood and lymphatic system disorders
LeukocytosisBlood and lymphatic system disorders
Cardiac arrestCardiac disorders
PalpitationsCardiac disorders
ConstipationGastrointestinal disorders
Urinary tract infectionInfections and infestations
Haptoglobin decreasedInvestigations
Decreased appetiteMetabolism and nutrition disorders
ArthralgiaMusculoskeletal and connective tissue disorders
Back painMusculoskeletal and connective tissue disorders
Flank painMusculoskeletal and connective tissue disorders
Pain in extremityMusculoskeletal and connective tissue disorders
AmnesiaNervous system disorders
DizzinessNervous system disorders
DysgeusiaNervous system disorders
HeadacheNervous system disorders
ParaesthesiaNervous system disorders
CoughRespiratory, thoracic and mediastinal disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
PruritusSkin and subcutaneous tissue disorders
Skin hyperpigmentationSkin and subcutaneous tissue disorders

Most-reported serious reactions: Pyrexia, Dyspnoea, Hypoxia, Pleural effusion, Respiratory failure.

Data from ClinicalTrials.gov NCT04165031 adverse events section.

Sponsor's own description

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.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

  1. RAS-targeted therapies: is the undruggable drugged?
    Moore AR, Rosenberg SC, McCormick F, Malek S. · · 2020 · cited 832× · PMID 32528145 · DOI 10.1038/s41573-020-0068-6
  2. KRAS mutation: from undruggable to druggable in cancer.
    Huang L, Guo Z, Wang F, Fu L. · · 2021 · cited 728× · PMID 34776511 · DOI 10.1038/s41392-021-00780-4
  3. Role of oncogenic KRAS in the prognosis, diagnosis and treatment of colorectal cancer.
    Zhu G, Pei L, Xia H, Tang Q, et al · · 2021 · cited 342× · PMID 34742312 · DOI 10.1186/s12943-021-01441-4
  4. Targeting KRAS(G12C): From Inhibitory Mechanism to Modulation of Antitumor Effects in Patients.
    Kim D, Xue JY, Lito P. · · 2020 · cited 179× · PMID 33065029 · DOI 10.1016/j.cell.2020.09.044
  5. Emerging strategies to target RAS signaling in human cancer therapy.
    Chen K, Zhang Y, Qian L, Wang P. · · 2021 · cited 164× · PMID 34301278 · DOI 10.1186/s13045-021-01127-w
  6. Targeting KRAS mutant cancers: from druggable therapy to drug resistance.
    Zhu C, Guan X, Zhang X, Luan X, et al · · 2022 · cited 159× · PMID 35922812 · DOI 10.1186/s12943-022-01629-2
  7. The path to the clinic: a comprehensive review on direct KRAS<sup>G12C</sup> inhibitors.
    Kwan AK, Piazza GA, Keeton AB, Leite CA. · · 2022 · cited 142× · PMID 35045886 · DOI 10.1186/s13046-021-02225-w
  8. Mechanisms of Resistance to KRAS<sup>G12C</sup>-Targeted Therapy.
    Akhave NS, Biter AB, Hong DS. · · 2021 · cited 112× · PMID 33820777 · DOI 10.1158/2159-8290.cd-20-1616

Verify or expand the search:

Other recruiting trials for Advanced Solid Tumor

Currently open trials in the same condition.

Other Eli Lilly and Company trials

Trials by the same sponsor.

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