Recruiting
Phase 1

LY4175408

Sponsor:

Eli Lilly and Company

Code:

NCT07046923

Conditions

Carcinoma, Non-Small-Cell Lung

Small Cell Lung Carcinoma

Endometrial Neoplasms

Neoplasm Metastasis

Triple Negative Breast Cancer

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

Interventions

LY4175408

Pembrolizumab

Carboplatin

Cisplatin

Study Details

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

Study ID

NCT07046923

Start date

Jul 28, 2025

Status verified date

Jun, 2026

Completion date

Jul, 2030

Anticipated

Primary completion date

Jul, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18+

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

240 participants

Anticipated

Allocation

Non randomized

Intervention Model

Sequential

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Phase 1a Dose Escalation (Cohort A1)

Escalating doses of LY4175408 administered intravenously (IV)

experimental: Phase 1a Dose Optimization (Cohort A2)

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

experimental: Phase 1b Dose Expansion (Cohort B1)

LY4175408 administered IV followed by pembrolizumab administered IV

experimental: Phase 1b Dose Expansion (Cohort B2)

LY4175408 administered IV followed by pembrolizumab administered IV and either carboplatin administered IV or cisplatin administered IV

experimental: Phase 1b Dose Expansion (Cohorts C1, C2 and C3)

LY4175408 administered IV

Interventions

LY4175408

IV infusion

Pembrolizumab

IV infusion

Carboplatin

IV infusion

Cisplatin

IV infusion

Primary outcome measure

  • Phase 1a-Number of Participants with Dose Limiting Toxicities of LY4175408 [ Time Frame: 1 Cycle (21 days) ]
  • Phase 1b-Overall Response Rate (ORR): Percentage of Participants with Best Response of Complete Response (CR) or Partial Response (PR) [ Time Frame: Baseline up to approximately 4 years ]

Central Contacts and Locations

Central contacts

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

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

Physicians interested in becoming principal investigators please contact

clinical_inquiry_hub@lilly.com

Locations

Stanford Medicine Cancer Center

Recruiting

Stanford, California, United States, 94305

Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute

Recruiting

Orlando, Florida, United States, 32827

Florida Cancer Specialists - Sarasota

Recruiting

Sarasota, Florida, United States, 34236

The University of Chicago Medical Center (UCMC)

Recruiting

Chicago, Illinois, United States, 60637

Community Health Network

Recruiting

Indianapolis, Indiana, United States, 46250

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02114

Washington University

Recruiting

St Louis, Missouri, United States, 63110

John Theurer Cancer Center At Hackensack UMC

Recruiting

Hackensack, New Jersey, United States, 07601

Columbia University

Recruiting

New York, New York, United States, 10032

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

Recruiting

New York, New York, United States, 10065

The Ohio State University (OSU) Wexner Medical Center

Recruiting

Columbus, Ohio, United States, 43210

Sarah Cannon Research Institute

Recruiting

Nashville, Tennessee, United States, 37203

MD Anderson Cancer Center

Recruiting

Houston, Texas, United States, 77030

START Mountain Region

Recruiting

West Valley City, Utah, United States, 84119

NEXT Virginia

Recruiting

Fairfax, Virginia, United States, 22031

More Information

Sponsor

Eli Lilly and Company

Last update posted

Jun 23, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-09. This information was provided to ClinicalTrials.gov by Eli Lilly and Company on 2026-06-23.