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 Sex
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, hearing loss, 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) or 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.
    Other names:
    • Folinic Acid
  • 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

University of Alabama at Birmingham
Birmingham 4049979, Alabama 4829764 35233

Mayo Clinic
Phoenix 5308655, Arizona 5551752 85054

City of Hope
Duarte 5344147, California 5332921 91010

University of California, Los Angeles (UCLA)
Los Angeles 5368361, California 5332921 90025

Yale University School of Medicine - Yale Cancer Center
New Haven 4839366, Connecticut 4831725 06520-8028

The University of Chicago Medical Center (UCMC)
Chicago 4887398, Illinois 4896861 60637

Indiana University (IU)
Indianapolis 4259418, Indiana 4921868 46202

Massachusetts General Hospital
Boston 4930956, Massachusetts 6254926 02114

Dana-Farber Cancer Institute
Boston 4930956, Massachusetts 6254926 02215

Henry Ford Health System
Detroit 4990729, Michigan 5001836 48202

South Texas Accelerated Research Therapeutics (START) Midwest
Grand Rapids 4994358, Michigan 5001836 49546

Columbia University
New York 5128581, New York 5128638 10032

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
New York 5128581, New York 5128638 10065

Duke University Medical Center
Durham 4464368, North Carolina 4482348 27710

Cleveland Clinic
Cleveland 5150529, Ohio 5165418 44195

University of Pittsburgh Medical Center
Pittsburgh 5206379, Pennsylvania 6254927 15213

Sarah Cannon Research Institute/SCRI
Nashville 4644585, Tennessee 4662168 37203

SCRI Oncology Partners
Nashville 4644585, Tennessee 4662168 37203

University of Texas Southwestern
Dallas 4684888, Texas 4736286 75244

MD Anderson Cancer Center
Houston 4699066, Texas 4736286 77030

South Texas Accelerated Research Therapeutics (START)
San Antonio 4726206, Texas 4736286 78229

Virginia Cancer Specialists
Fairfax 4758023, Virginia 6254928 22031

Swedish Cancer Institute (SCI)
Seattle 5809844, Washington 5815135 98104

More Details

NCT ID
NCT06607185
Status
Recruiting
Sponsor
Eli Lilly and Company

Study Contact

Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
1-317-615-4559
LillyTrials@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