A Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

Purpose

The main purpose of the study is to assess whether the study drug, LY4066434, is safe and tolerable when administered to participants with locally advanced or metastatic solid tumors with certain KRAS mutations. LY4066434 will be given alone or in combination with other treatments. The study will have 2 parts: monotherapy dose escalation and dose optimization. The study is expected to last up to approximately 5 years.

Conditions

  • Pancreatic Ductal Adenocarcinoma
  • Non-small Cell Lung Cancer
  • Colorectal Cancer
  • Advanced Solid Tumor
  • Metastatic Solid Tumor

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Have evidence of KRAS G12C, G12D, G12V, G12A, G12S, or G13D mutation in tumor tissue or circulating tumor DNA - Histological or cytologically proven diagnosis of a locally advanced, unresectable, and/or metastatic solid tumor cancer - Have measurable disease per RECIST 1.1 - Have an ECOG performance status of ≤1 - Must not be pregnant and/or planning to breastfeed during the trial or within 180 days of the last dose of trial intervention - Must be able to swallow tablets - Participants with asymptomatic or treated CNS disease may be eligible

Exclusion Criteria

  • Have known active CNS metastases and/or carcinomatous meningitis - Have any unresolved toxicities from prior therapy greater than NCI CTCAE Version 5.0 Grade 1 at the time of starting trial treatment, except for alopecia, peripheral neuropathy and ongoing endocrinopathies controlled on appropriate replacement therapy - Have significant cardiovascular disease defined as unstable angina or acute coronary syndrome, history of myocardial infarction, known left ventricular ejection fraction or heart failure, uncontrolled or symptomatic arrhythmias. - Have known active hepatitis B virus (HBV), hepatitis C virus (HCV) and untreated HIV infection - Have other active malignancy unless in remission with life expectancy greater than 2 years. - Have active uncontrolled systemic bacterial, viral, fungal, or parasitic infection - Have history of non-infectious pneumonitis/interstitial lung disease that received steroids or has current clinically significant pneumonitis/interstitial lung disease

Study Design

Phase
Phase 1
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Sequential Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Experimental
LY4066434 Monotherapy Dose Escalation 		Escalating doses of LY4066434 administered orally.
  • Drug: LY4066434.
    Administered orally.
Experimental
LY4066434 Dose Optimization 		LY4066434 administered orally either alone or with another investigational agent.
  • Drug: LY4066434.
    Administered orally.
  • Drug: Cetuximab
    Administered intravenously.
  • Drug: Nab paclitaxel
    Administered intravenously.
  • Drug: Gemcitabine
    Administered intravenously.
  • Drug: Oxaliplatin
    Administered intravenously.
  • Drug: Leucovorin
    Administered intravenously.
  • Drug: Irinotecan
    Administered intravenously.
  • Drug: 5Fluorouracil
    Administered intravenously.
  • Drug: Carboplatin
    Administered intravenously.
  • Drug: Cisplatin
    Administered intravenously.
  • Drug: Pemetrexed
    Administered intravenously.
  • Drug: Pembrolizumab
    Administered intravenously.

Recruiting Locations

City of Hope
Duarte, California 91010

Yale University School of Medicine - Yale Cancer Center
New Haven, Connecticut 06520-8028

Indiana University (IU)
Indianapolis, Indiana 46202

Massachusetts General Hospital
Boston, Massachusetts 02114

Dana-Farber Cancer Institute
Boston, Massachusetts 02215

South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids, Michigan 49546

Columbia University
New York, New York 10032

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York, New York 10065

Duke University Medical Center
Durham, North Carolina 27710

Cleveland Clinic
Cleveland, Ohio 44195

University of Pittsburgh Medical Center
Pittsburgh, Pennsylvania 15232

SCRI Oncology Partners
Nashville, Tennessee 37203

University of Texas Southwestern
Dallas, Texas 75238

MD Anderson Cancer Center
Houston, Texas 77030

South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas 78229

Virginia Cancer Specialists
Fairfax, Virginia 22031

More Details

NCT ID
NCT06607185
Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or
13176154559
clinical_inquiry_hub@lilly.com

For help using this page: trialstoday@researchmatch.org or call 855-514-7001

ResearchMatch is funded in part by the National Institutes of Health (NIH) Clinical and Translational Science Award (CTSA) program, led by the NIH’s National Center for Advancing Translational Sciences (NCATS), grants UL1TR000445 and 1U54RR032646-01, and grant U24TR001579 from NCATS and the National Library of Medicine. The content of this website is solely the responsibility of ResearchMatch and Vanderbilt University and does not necessarily represent the official views of the NIH, NCATS, or NLM.

Vanderbilt University Medical Center