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

NCT ID: NCT06607185

Last Updated: 2025-12-22

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

750 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-10-21

Study Completion Date

2030-01-31

Brief Summary

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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.

Detailed Description

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Conditions

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

Keywords

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KRAS KRAS mutation KRASG12C KRASG12D KRASG12V KRASG12S KRASG12A KRASG13D LY4066434 Targeted therapy Lung cancer Pancreas cancer Colon cancer Rectal cancer Colorectal cancer Ovarian cancer Endometrial cancer Cholangiocarcinoma Esophageal cancer KRAS-mutant tumor PanKRAS Pan KRAS

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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LY4066434 Monotherapy Dose Escalation

Escalating doses of LY4066434 administered orally.

Group Type EXPERIMENTAL

LY4066434.

Intervention Type DRUG

Administered orally.

LY4066434 Dose Optimization

LY4066434 administered orally either alone or with another investigational agent.

Group Type EXPERIMENTAL

LY4066434.

Intervention Type DRUG

Administered orally.

Cetuximab

Intervention Type DRUG

Administered intravenously.

Nab paclitaxel

Intervention Type DRUG

Administered intravenously.

Gemcitabine

Intervention Type DRUG

Administered intravenously.

Oxaliplatin

Intervention Type DRUG

Administered intravenously.

Leucovorin

Intervention Type DRUG

Administered intravenously.

Irinotecan

Intervention Type DRUG

Administered intravenously.

5Fluorouracil

Intervention Type DRUG

Administered intravenously.

Carboplatin

Intervention Type DRUG

Administered intravenously.

Cisplatin

Intervention Type DRUG

Administered intravenously.

Pemetrexed

Intervention Type DRUG

Administered intravenously.

Pembrolizumab

Intervention Type DRUG

Administered intravenously.

Interventions

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LY4066434.

Administered orally.

Intervention Type DRUG

Cetuximab

Administered intravenously.

Intervention Type DRUG

Nab paclitaxel

Administered intravenously.

Intervention Type DRUG

Gemcitabine

Administered intravenously.

Intervention Type DRUG

Oxaliplatin

Administered intravenously.

Intervention Type DRUG

Leucovorin

Administered intravenously.

Intervention Type DRUG

Irinotecan

Administered intravenously.

Intervention Type DRUG

5Fluorouracil

Administered intravenously.

Intervention Type DRUG

Carboplatin

Administered intravenously.

Intervention Type DRUG

Cisplatin

Administered intravenously.

Intervention Type DRUG

Pemetrexed

Administered intravenously.

Intervention Type DRUG

Pembrolizumab

Administered intravenously.

Intervention Type DRUG

Other Intervention Names

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Folinic Acid

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Eli Lilly and Company

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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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)

Role: STUDY_DIRECTOR

Eli Lilly and Company

Locations

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University of Alabama at Birmingham

Birmingham, Alabama, United States

Site Status RECRUITING

Mayo Clinic

Phoenix, Arizona, United States

Site Status RECRUITING

City of Hope

Duarte, California, United States

Site Status RECRUITING

University of California, Los Angeles (UCLA)

Los Angeles, California, United States

Site Status RECRUITING

University of Colorado Denver

Denver, Colorado, United States

Site Status NOT_YET_RECRUITING

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, United States

Site Status RECRUITING

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, United States

Site Status RECRUITING

Indiana University (IU)

Indianapolis, Indiana, United States

Site Status RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, United States

Site Status RECRUITING

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Site Status RECRUITING

Henry Ford Health System

Detroit, Michigan, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, United States

Site Status RECRUITING

Mayo Clinic - Rochester

Rochester, Minnesota, United States

Site Status NOT_YET_RECRUITING

Columbia University

New York, New York, United States

Site Status RECRUITING

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status RECRUITING

Duke University Medical Center

Durham, North Carolina, United States

Site Status RECRUITING

Cleveland Clinic

Cleveland, Ohio, United States

Site Status RECRUITING

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, United States

Site Status NOT_YET_RECRUITING

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Sarah Cannon Research Institute/SCRI

Nashville, Tennessee, United States

Site Status RECRUITING

SCRI Oncology Partners

Nashville, Tennessee, United States

Site Status RECRUITING

University of Texas Southwestern

Dallas, Texas, United States

Site Status RECRUITING

MD Anderson Cancer Center

Houston, Texas, United States

Site Status RECRUITING

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, United States

Site Status RECRUITING

Virginia Cancer Specialists

Fairfax, Virginia, United States

Site Status RECRUITING

Swedish Cancer Institute (SCI)

Seattle, Washington, United States

Site Status RECRUITING

Universite Libre de Bruxelles (ULB) - Institut Jules Bordet

Brussels, , Belgium

Site Status RECRUITING

Cliniques universitaires Saint-Luc

Brussels, , Belgium

Site Status RECRUITING

UZ Gent

Ghent, , Belgium

Site Status RECRUITING

Cancer Institute & Hospital, Chinese Academy of Medical Sciences

Beijing, , China

Site Status NOT_YET_RECRUITING

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, , China

Site Status NOT_YET_RECRUITING

Shandong Province Tumor Hospital

Jinan, , China

Site Status NOT_YET_RECRUITING

Shanghai East Hospital, Tongji University

Shanghai, , China

Site Status NOT_YET_RECRUITING

Tianjin Medical University Cancer Institute & Hospital

Tianjin, , China

Site Status NOT_YET_RECRUITING

Centre Leon Berard

Lyon, , France

Site Status NOT_YET_RECRUITING

Institut Gustave Roussy

Villejuif, , France

Site Status NOT_YET_RECRUITING

Charite Universitaetsmedizin Berlin

Berlin, , Germany

Site Status NOT_YET_RECRUITING

Krankenhaus Nordwest GmbH

Frankfurt, , Germany

Site Status RECRUITING

Asklepios Kliniken Hamburg GmbH - Asklepios Klinik Altona

Hamburg, , Germany

Site Status RECRUITING

SLK-Kliniken Heilbronn GmBH

Heilbronn, , Germany

Site Status RECRUITING

Universitaetsklinikum Wuerzburg

Würzburg, , Germany

Site Status RECRUITING

Centro Ricerche Cliniche di Verona s.r.l.

Verona, , Italy

Site Status RECRUITING

National Cancer Center Hospital East

Chiba, , Japan

Site Status RECRUITING

Kyoto University Hospital

Kyoto, , Japan

Site Status RECRUITING

Shizuoka Cancer Center

Shizuoka, , Japan

Site Status RECRUITING

National Cancer Center Hospital

Tokyo, , Japan

Site Status RECRUITING

Cancer Institute Hospital of JFCR

Tokyo, , Japan

Site Status RECRUITING

Hospital del Mar

Barcelona, , Spain

Site Status RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, , Spain

Site Status RECRUITING

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, , Spain

Site Status RECRUITING

Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Site Status RECRUITING

Hospital Universitario 12 de Octubre

Madrid, , Spain

Site Status RECRUITING

Hospital Regional Universitario de Malaga

Málaga, , Spain

Site Status RECRUITING

National Taiwan University Hospital Hsin-Chu Branch

Hsinchu, , Taiwan

Site Status RECRUITING

National Taiwan University Hospital

Taipei, , Taiwan

Site Status RECRUITING

Countries

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United States Belgium China France Germany Italy Japan Spain Taiwan

Central Contacts

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Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or

Role: CONTACT

Phone: 1-317-615-4559

Email: [email protected]

Physicians interested in becoming principal investigators please contact

Role: CONTACT

Email: [email protected]

Related Links

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http://trials.lilly.com/en-US/trial/533775

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

Other Identifiers

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J5Q-OX-JRDA

Identifier Type: OTHER

Identifier Source: secondary_id

27237

Identifier Type: -

Identifier Source: org_study_id