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

NCT06607185 | Active Not Recruiting Phase 1 FDA Drug

• 2 other identifiers: 27237J5Q-OX-JRDA
• Study Type: interventional
• Target: 750
• Locations: 9 countries
• Sites: 56

Brief Summary

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

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Number of Participants with Dose-limiting Toxicities (DLTs)

  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

  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 Outcomes (11)

• Overall Response Rate (ORR)

  Up to approximately 5 years

• Best Overall Response (BOR)

  Up to approximately 5 years

• Duration of Response (DOR)

  Up to approximately 5 years

• Disease Control Rate (DCR)

  Up to approximately 5 years

• Time to Response (TTR)

  Up to approximately 5 years

Study Arms (2)

LY4066434 Monotherapy Dose Escalation

EXPERIMENTAL

Escalating doses of LY4066434 administered orally.

Drug: LY4066434.

LY4066434 Dose Optimization

EXPERIMENTAL

LY4066434 administered orally either alone or with another investigational agent.

Drug: LY4066434.; Drug: Cetuximab; Drug: Nab paclitaxel; Drug: Gemcitabine; Drug: Oxaliplatin; Drug: Leucovorin; Drug: Irinotecan; Drug: 5Fluorouracil; Drug: Carboplatin; Drug: Cisplatin; Drug: Pemetrexed; Drug: Pembrolizumab

Interventions

LY4066434. DRUG

Administered orally.

LY4066434 Dose Optimization; LY4066434 Monotherapy Dose Escalation

Cetuximab DRUG

Administered intravenously.

LY4066434 Dose Optimization

Nab paclitaxel DRUG

Administered intravenously.

LY4066434 Dose Optimization

Gemcitabine DRUG

Administered intravenously.

LY4066434 Dose Optimization

Oxaliplatin DRUG

Administered intravenously.

LY4066434 Dose Optimization

Leucovorin DRUG

Administered intravenously.

Also known as: Folinic Acid

LY4066434 Dose Optimization

Irinotecan DRUG

Administered intravenously.

LY4066434 Dose Optimization

5Fluorouracil DRUG

Administered intravenously.

LY4066434 Dose Optimization

Carboplatin DRUG

Administered intravenously.

LY4066434 Dose Optimization

Cisplatin DRUG

Administered intravenously.

LY4066434 Dose Optimization

Pemetrexed DRUG

Administered intravenously.

LY4066434 Dose Optimization

Pembrolizumab DRUG

Administered intravenously.

LY4066434 Dose Optimization

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (56)

University of Alabama at Birmingham

Birmingham, Alabama, 35233, United States

Location

Mayo Clinic

Phoenix, Arizona, 85054, United States

Location

City of Hope

Duarte, California, 91010, United States

Location

University of California, Los Angeles (UCLA)

Santa Monica, California, 90404, United States

Location

University of Colorado Denver

Denver, Colorado, 80220, United States

Location

Yale University School of Medicine - Yale Cancer Center

New Haven, Connecticut, 06520-8028, United States

Location

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, 60637, United States

Location

Indiana University (IU)

Indianapolis, Indiana, 46202, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

South Texas Accelerated Research Therapeutics (START) Midwest

Grand Rapids, Michigan, 49546, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

Columbia University

New York, New York, 10032, United States

Location

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

New York, New York, 10065, United States

Location

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

University of Oklahoma - Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh Medical Center

Pittsburgh, Pennsylvania, 15213, United States

Location

Sarah Cannon Research Institute/SCRI

Nashville, Tennessee, 37203, United States

Location

SCRI Oncology Partners

Nashville, Tennessee, 37203, United States

Location

University of Texas Southwestern

Dallas, Texas, 75244, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas, 78229, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

Swedish Cancer Institute (SCI)

Seattle, Washington, 98104, United States

Location

Universite Libre de Bruxelles (ULB) - Institut Jules Bordet

Brussels, 1070, Belgium

Location

Cliniques universitaires Saint-Luc

Brussels, 1200, Belgium

Location

UZ Gent

Ghent, 9000, Belgium

Location

Cancer Institute & Hospital, Chinese Academy of Medical Sciences

Beijing, 100021, China

Location

The First Affiliated Hospital, College of Medicine, Zhejiang University

Hangzhou, 310006, China

Location

Shandong Province Tumor Hospital

Jinan, 250117, China

Location

Shanghai East Hospital, Tongji University

Shanghai, 0200120, China

Location

Tianjin Medical University Cancer Institute & Hospital

Tianjin, 300060, China

Location

Centre Leon Berard

Lyon, 69373, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Charite Universitaetsmedizin Berlin

Berlin, 10117, Germany

Location

Krankenhaus Nordwest GmbH

Frankfurt, 60488, Germany

Location

Asklepios Kliniken Hamburg GmbH - Asklepios Klinik Altona

Hamburg, 22763, Germany

Location

SLK-Kliniken Heilbronn GmBH

Heilbronn, 74078, Germany

Location

Universitaetsklinikum Wuerzburg

Würzburg, 97080, Germany

Location

Centro Ricerche Cliniche di Verona s.r.l.

Verona, 37134, Italy

Location

National Cancer Center Hospital East

Chiba, 277-8577, Japan

Location

Kyoto University Hospital

Kyoto, 606-8507, Japan

Location

Shizuoka Cancer Center

Shizuoka, 411-8777, Japan

Location

National Cancer Center Hospital

Tokyo, 104-0045, Japan

Location

Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

Location

Institut Catala d'Oncologia - L'Hospitalet

Barcelona, 08908, Spain

Location

Hospital General Universitario Gregorio Maranon

Madrid, 28007, Spain

Location

Hospital Universitario Ramon y Cajal

Madrid, 28034, Spain

Location

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

National Taiwan University Hospital Hsin-Chu Branch

Hsinchu, 300195, Taiwan

Location

National Taiwan University Hospital

Taipei, 10016, Taiwan

Location

Related Links

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

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms; Neoplasm Metastasis; Lung Neoplasms; Pancreatic Neoplasms; Colonic Neoplasms; Rectal Neoplasms; Ovarian Neoplasms; Endometrial Neoplasms; Cholangiocarcinoma; Esophageal Neoplasms

Interventions

Cetuximab; Taxes; Gemcitabine; Oxaliplatin; Leucovorin; Irinotecan; Fluorouracil; Carboplatin; Cisplatin; Pemetrexed; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Endocrine Gland Neoplasms; Pancreatic Diseases; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Head and Neck Neoplasms; Esophageal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Economics; Health Care Economics and Organizations; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Coordination Complexes; Organic Chemicals; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Camptothecin; Alkaloids; Uracil; Pyrimidinones; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Dicarboxylic

Study Officials

• 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

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 19, 2024
• First Posted: September 23, 2024
• Study Start: October 21, 2024
• Primary Completion (Estimated): January 1, 2030
• Study Completion (Estimated): January 1, 2030
• Last Updated: April 22, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

TW (2); IT (1); BE (3); JP (5); FR (2); DE (5); ES (7); US (26); CN (5)