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RecruitingInterventionalPhase 1

A First-in-Human, Phase 1a/1b Trial to Assess the Safety, Tolerability and Preliminary Efficacy of LY4175408, an Antibody Drug Conjugate Targeting Protein Tyrosine Kinase 7-Expressing Tumor Cells, in Participants With Selected Advanced Solid Tumors

NCT ID: NCT07046923Sponsor: Eli Lilly and CompanyLast updated: 2026-06-02

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.

Arms & interventions

  • DrugLY4175408

    IV infusion

  • DrugPembrolizumab

    IV infusion

  • DrugCarboplatin

    IV infusion

  • DrugCisplatin

    IV infusion

Outcome measures

Primary

  • 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)

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

    Time frame: Baseline up to approximately 4 years

Secondary

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

    Time frame: 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)

    Time frame: First 4 cycles (84 days)

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

    Time frame: Baseline up to approximately 4 years

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

    Time frame: Baseline up to approximately 4 years

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

    Time frame: Baseline up to approximately 4 years

  • Phase 1a and 1b-Disease Control Rate (DCR)

    Time frame: Baseline up to approximately 4 years

  • Phase 1a and 1b-Duration of Response (DOR)

    Time frame: Baseline up to approximately 4 years

Eligibility criteria

Sex: AllAge: 18 Years and olderHealthy volunteers: No
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 locations (15)

Stanford Medicine Cancer Center

Stanford, California, 94305

Recruiting

Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute

Orlando, Florida, 32827

Recruiting

Florida Cancer Specialists - Sarasota

Sarasota, Florida, 34236

Recruiting

The University of Chicago Medical Center (UCMC)

Chicago, Illinois, 60637

Recruiting

Community Health Network

Indianapolis, Indiana, 46250

Not Yet Recruiting

Massachusetts General Hospital

Boston, Massachusetts, 02114

Recruiting

Washington University

St Louis, Missouri, 63110

Recruiting

John Theurer Cancer Center At Hackensack UMC

Hackensack, New Jersey, 07601

Recruiting

Columbia University

New York, New York, 10032

Recruiting

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

New York, New York, 10065

Recruiting

The Ohio State University (OSU) Wexner Medical Center

Columbus, Ohio, 43210

Recruiting

Sarah Cannon Research Institute

Nashville, Tennessee, 37203

Recruiting

MD Anderson Cancer Center

Houston, Texas, 77030

Recruiting

START Mountain Region

West Valley City, Utah, 84119

Recruiting

NEXT Virginia

Fairfax, Virginia, 22031

Recruiting
A Study of LY4175408 in Participants With Advanced Cancer | Cancerify