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NCT07046923PHASE1Recruiting

A Study of LY4175408 in Participants With Advanced Cancer

Eli Lilly and Company

Start Date

7/28/2025

Completion Date

7/1/2030

Summary

The purpose of this study is to measure the safety and efficacy of LY4175408 in participants with selected advanced cancer. In addition, this study will evaluate how much LY4175408 gets into the bloodstream, how it is broken down, and how long it takes the body to get rid of it. Participation could last up to 4 years.

Eligibility Criteria

Age Range: 18 years to No maximum

Inclusion Criteria: * Have one of the following advanced or metastatic solid tumor cancers: * Non-small cell lung cancer (NSCLC) * Small cell lung cancer (SCLC) * Endometrial cancer * Triple negative breast cancer (TNBC) (characterized by HR-negative disease and HER2-negative expression according to American Society of Clinical Oncology (ASCO) - College of American Pathologists guidelines). * Received all standard therapies for which the individual was deemed to be an appropriate candidate by the treating investigator (except in Cohort B1 and B2 expansion, which require participants who are treatment naive in the advanced metastatic setting); OR the individual is refusing the remaining most appropriate standard of care treatment; OR there is no standard therapy available for the disease. * Eastern Cooperative Oncology Group (ECOG) performance status of greater than or equal to (≤) 1. * For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B/C): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. * Cohorts B1/B2: NSCLC with no known actionable genomic alterations. ≤2 prior lines of systemic therapy for advanced or metastatic disease in safety lead-in; no prior systemic therapy in expansion Exclusion Criteria: * Prior treatment with a protein tyrosine kinase 7 (PTK7) antibody-drug conjugate (ADC) with a topoisomerase I inhibitor as payload (prior therapy with a PTK7 ADC with a non-topoisomerase I inhibitor payload OR non-PTK7 ADC with any payload is permitted). Prior topoisomerase I-based ADCs are not allowed in cohorts A2, B1 or B2. * Any serious unresolved toxicities from prior therapy. * Individual with known or suspected history of uncontrolled central nervous system (CNS) metastases. * Individual with active uncontrolled systemic bacterial, viral, fungal, or parasitic infection. * Significant cardiovascular disease. * Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) \> 470 milliseconds (ms) * History of pneumonitis/interstitial lung disease. * Individuals who are pregnant, breastfeeding, or plan to breastfeed during the trial or within 30 days of the last dose of trial intervention.

Interventions

DRUG

LY4175408

DRUG

Pembrolizumab

DRUG

Carboplatin

DRUG

Cisplatin

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Conditions

Carcinoma, Non-Small-Cell LungSmall Cell Lung CarcinomaEndometrial NeoplasmsNeoplasm MetastasisTriple Negative Breast Cancer

Locations

Stanford Medicine Cancer Center

Stanford, California 94305

United States

Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute

Orlando, Florida 32827

United States

Florida Cancer Specialists - Sarasota

Sarasota, Florida 34236

United States

The University of Chicago Medical Center (UCMC)

Chicago, Illinois 60637

United States

Community Health Network

Indianapolis, Indiana 46250

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Washington University

St Louis, Missouri 63110

United States

John Theurer Cancer Center At Hackensack UMC

Hackensack, New Jersey 07601

United States

Columbia University

New York, New York 10032

United States

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

New York, New York 10065

United States

The Ohio State University (OSU) Wexner Medical Center

Columbus, Ohio 43210

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

MD Anderson Cancer Center

Houston, Texas 77030

United States

START Mountain Region

West Valley City, Utah 84119

United States

NEXT Virginia

Fairfax, Virginia 22031

United States

West China Hospital, Sichuan University

Chengdu, 610041

China

Shanghai East Hospital, Tongji University

Shanghai, 0200120

China

Tongji Hospital - Tongji Medical College of HUST

Wuhan, 430030

China

Centre Leon Berard

Lyon, 69373

France

Institut Gustave Roussy

Villejuif, 94805

France

Kyoto University Hospital

Kyoto, 606-8507

Japan

National Cancer Center Hospital

Tokyo, 104-0045

Japan

Cancer Institute Hospital of JFCR

Tokyo, 135-8550

Japan

Severance Hospital, Yonsei University Health System

Seoul, 03722

South Korea

Samsung Medical Center

Seoul, 06351

South Korea

Hospital Universitario Vall d'Hebron

Barcelona, 08035

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain