A Study of LY4175408 in Participants With Advanced Cancer

NCT07046923 | Recruiting Phase 1 DMC FDA Drug

• 3 other identifiers: 27401J6D-MC-JSDA2025-521916-20-00
• Study Type: interventional
• Target: 240
• Locations: 6 countries
• Sites: 25

Brief 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.

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Endometrial Neoplasms; Neoplasm Metastasis; Triple Negative Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408

  1 Cycle (21 days)

• Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR)

  Per investigator assessed Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1)

  Baseline up to approximately 4 years

Secondary Outcomes (7)

• Phase 1a and 1b-Pharmacokinetics (PK): Minimum Plasma Concentration (Cmin) of LY4175408 (total antibody, conjugated antibody, free payload)

  First 4 cycles (84 days)

• Phase 1a and 1b-PK: Area under the Concentration versus Time Curve (AUC) of LY4175408 (total antibody, conjugated antibody, free payload)

  First 4 cycles (84 days)

• Phase 1a-ORR: Percentage of Participants with Best Response of CR or PR

  Baseline up to approximately 4 years

• Phase 1a and 1b-Time to Response (TTR)

  Baseline up to approximately 4 years

• Phase 1a and 1b-Progression-free Survival (PFS)

  Baseline up to approximately 4 years

Study Arms (3)

Phase 1a Dose Escalation (Cohort A1)

EXPERIMENTAL

Escalating doses of LY4175408 administered intravenously (IV)

Drug: LY4175408

Phase 1a Dose Optimization (Cohort A2)

EXPERIMENTAL

Two or more doses of LY4175408 (evaluated during dose escalation) administered IV

Drug: LY4175408

Phase 1b Dose Expansion (Cohort B)

EXPERIMENTAL

LY4175408 administered IV

Drug: LY4175408

Interventions

LY4175408 DRUG

IV infusion

Phase 1a Dose Escalation (Cohort A1); Phase 1a Dose Optimization (Cohort A2); Phase 1b Dose Expansion (Cohort B)

Eligibility Criteria

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

You may qualify if:

• 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; 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 ≤1.
• For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

You may not qualify if:

• 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).
• 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.

Sponsors & Collaborators

• Eli Lilly and Company: lead

Study Sites (25)

Stanford Cancer Center

Stanford, California, 94305, United States

RECRUITING

Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute

Orlando, Florida, 32827, United States

RECRUITING

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34236, United States

RECRUITING

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, 60637, United States

RECRUITING

Community Health Network

Indianapolis, Indiana, 46250, United States

NOT YET RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Washington University

St Louis, Missouri, 63110, United States

RECRUITING

John Theurer Cancer Center At Hackensack UMC

Hackensack, New Jersey, 07601, United States

RECRUITING

Columbia University

New York, New York, 10032, United States

RECRUITING

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

New York, New York, 10065, United States

RECRUITING

The Ohio State University (OSU) Wexner Medical Center

Columbus, Ohio, 43210, United States

RECRUITING

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

RECRUITING

MD Anderson Cancer Center

Houston, Texas, 77030, United States

RECRUITING

START Mountain Region

West Valley City, Utah, 84119, United States

RECRUITING

NEXT Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Shanghai East Hospital, Tongji University

Shanghai, 0200120, China

NOT YET RECRUITING

Centre Leon Berard

Lyon, 69373, France

RECRUITING

Institut Gustave Roussy

Villejuif, 94805, France

RECRUITING

Kyoto University Hospital

Kyoto, 606-8507, Japan

RECRUITING

National Cancer Center Hospital

Tokyo, 104-0045, Japan

RECRUITING

Cancer Institute Hospital of JFCR

Tokyo, 135-8550, Japan

RECRUITING

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

RECRUITING

Samsung Medical Center

Seoul, 06351, South Korea

RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

RECRUITING

Hospital Universitario 12 de Octubre

Madrid, 28041, Spain

RECRUITING

Related Links

• A Study of LY4175408 in Participants With Advanced Cancer

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Small Cell Lung Carcinoma; Endometrial Neoplasms; Neoplasm Metastasis; Triple Negative Breast Neoplasms

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Breast Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

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

Central Study Contacts

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

CONTACT

1-317-615-4559; LillyTrials@Lilly.com

Physicians interested in becoming principal investigators please contact

CONTACT

clinical_inquiry_hub@lilly.com

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: June 24, 2025
• First Posted: July 2, 2025
• Study Start: July 28, 2025
• Primary Completion (Estimated): July 1, 2030
• Study Completion (Estimated): July 1, 2030
• Last Updated: April 17, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (15); KR (2); ES (2); JP (3); CN (1); FR (2)