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

July 17, 2026 updated by: Eli Lilly and Company

A Phase 1a/1b Study of the Pan-KRAS Inhibitor LY4066434 in Participants With KRAS Mutant Solid Tumors

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
750

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • Belgium
      • Brussels, Belgium, 1200
        • Cliniques universitaires Saint-Luc
      • Brussels, Belgium, 1070
        • Universite Libre de Bruxelles (ULB) - Institut Jules Bordet
      • Ghent, Belgium, 9000
        • UZ Gent
  • France
      • Lyon, France, 69373
        • Centre Léon Bérard
  • Germany
      • Frankfurt, Germany, 60488
        • Krankenhaus Nordwest GmbH
      • Hamburg, Germany, 22763
        • Asklepios Kliniken Hamburg GmbH - Asklepios Klinik Altona
      • Heilbronn, Germany, 74078
        • SLK-Kliniken Heilbronn GmbH
      • Würzburg, Germany, 97080
        • Universitaetsklinikum Wuerzburg
  • Italy
      • Verona, Italy, 37134
        • Centro Ricerche Cliniche di Verona s.r.l.
  • Japan
      • Chiba, Japan, 277-8577
        • National Cancer Center Hospital East
      • Kyoto, Japan, 606-8507
        • Kyoto University Hospital
      • Shizuoka, Japan, 411-8777
        • Shizuoka Cancer Center
      • Tokyo, Japan, 104-0045
        • National Cancer Center Hospital
      • Tokyo, Japan, 135-8550
        • Cancer Institute Hospital of JFCR
  • Spain
      • Barcelona, Spain, 08003
        • Hospital Del Mar
      • Barcelona, Spain, 08035
        • Hospital Universitario Vall d'Hebron
      • Barcelona, Spain, 08908
        • Institut Català d'Oncologia - L'Hospitalet
      • Madrid, Spain, 28034
        • Hospital Universitario Ramon y Cajal
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28007
        • Hospital General Universitario Gregorio Marañón
      • Málaga, Spain, 29010
        • Hospital Regional Universitario de Málaga
  • Taiwan
      • Hsinchu, Taiwan, 300195
        • National Taiwan University Hospital Hsin-Chu Branch
      • Taipei, Taiwan, 10016
        • National Taiwan University Hospital
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35233
        • University of Alabama at Birmingham
    • Arizona
      • Phoenix, Arizona, United States, 85054
        • Mayo Clinic
    • California
      • Duarte, California, United States, 91010
        • City of Hope
      • Santa Monica, California, United States, 90404
        • University of California, Los Angeles (UCLA)
    • Connecticut
      • New Haven, Connecticut, United States, 06520-8028
        • Yale University School of Medicine - Yale Cancer Center
    • Illinois
      • Chicago, Illinois, United States, 60637
        • The University of Chicago Medical Center (UCMC)
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University (IU)
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Dana-Farber Cancer Institute
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Michigan
      • Grand Rapids, Michigan, United States, 49546
        • South Texas Accelerated Research Therapeutics (START) Midwest
    • New York
      • New York, New York, United States, 10032
        • Columbia University
      • New York, New York, United States, 10065
        • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Durham, North Carolina, United States, 27710
        • Duke University Medical Center
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15213
        • University of Pittsburgh Medical Center
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Sarah Cannon Research Institute/SCRI
      • Nashville, Tennessee, United States, 37203
        • SCRI Oncology Partners
    • Texas
      • Dallas, Texas, United States, 75244
        • University of Texas Southwestern
      • Houston, Texas, United States, 77030
        • MD Anderson Cancer Center
      • San Antonio, Texas, United States, 78229
        • South Texas Accelerated Research Therapeutics (START)
    • Virginia
      • Fairfax, Virginia, United States, 22031
        • Virginia Cancer Specialists
    • Washington
      • Seattle, Washington, United States, 98104
        • Swedish Cancer Institute (SCI)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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: Carboplatin
Administered intravenously.
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: Cisplatin
Administered intravenously.
Drug: Pemetrexed
Administered intravenously.
Drug: Pembrolizumab
Administered intravenously.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants with Dose-limiting Toxicities (DLTs)
Time Frame: During the first cycle of LY4066434 treatment (up to 28 days)
During the first cycle of LY4066434 treatment (up to 28 days)
Number of Participants with One or More Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Event(s) (SAEs) Considered by the Investigator to be Related to Study Drug Administration
Time Frame: Up to approximately 5 years
A summary of TEAEs, SAEs and other non-serious adverse events (AEs), regardless of causality, will be reported in the Reported Adverse Events module.
Up to approximately 5 years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Overall Response Rate (ORR)
Time Frame: Up to approximately 5 years
ORR as assessed by investigator per Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST v1.1)
Up to approximately 5 years
Best Overall Response (BOR)
Time Frame: Up to approximately 5 years
BOR as assessed by investigator per RECIST v1.1
Up to approximately 5 years
Duration of Response (DOR)
Time Frame: Up to approximately 5 years
DOR as assessed by investigator per RECIST v1.1
Up to approximately 5 years
Disease Control Rate (DCR)
Time Frame: Up to approximately 5 years
DCR as assessed by investigator per RECIST v1.1
Up to approximately 5 years
Time to Response (TTR)
Time Frame: Up to approximately 5 years
TTR as assessed by investigator per RECIST v1.1
Up to approximately 5 years
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 Alone
Time Frame: Predose through Day 168
PK: Cmax of LY4066434
Predose through Day 168
Pharmacokinetics (PK): Maximum Observed Concentration (Cmax) of LY4066434 in Combination With Other Agents
Time Frame: Predose through Day 168
PK: Cmax of LY4066434
Predose through Day 168
PK: Time to Maximum Concentration (Tmax) of LY4066434 Alone
Time Frame: Predose through Day 168
PK: Tmax of LY4066434
Predose through Day 168
PK: Time to Maximum Concentration (Tmax) of LY4066434 in Combination With Other Agents
Time Frame: Predose through Day 168
PK: Tmax of LY4066434
Predose through Day 168
PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 Alone
Time Frame: Predose through Day 168
PK: AUC of LY4066434
Predose through Day 168
PK: Area Under the Concentration Versus Time Curve (AUC) of LY4066434 in Combination With Other Agents
Time Frame: Predose through Day 168
PK: AUC of LY4066434
Predose through Day 168

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 21, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
January 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
January 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 19, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 19, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 23, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
July 20, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 17, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 27237
  • J5Q-OX-JRDA (Other Identifier: Eli Lilly and Company)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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