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Recruiting

NCT Number: NCT07046923

A Study of LY4175408 in Participants With Advanced Cancer

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.

Recruiting

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Key information

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LY4175408

Drug

IV infusion

Pembrolizumab

Drug

IV infusion

carboplatin

Drug

IV infusion

Cisplatin

Drug

IV infusion

Primary outcomes

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

    Time frame: 1 Cycle (21 days)

  2. 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

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

Secondary outcomes

  1. 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)

  2. 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)

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

    Time frame: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Time frame: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Time frame: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Time frame: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Time frame: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

Study contacts

Contact information is provided by the study sponsor or research team.

Physicians interested in becoming principal investigators please contact

CONTACT

[email protected]

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

CONTACT

[email protected]

1-317-615-4559

Sponsors and collaborators

Lead sponsor

Eli Lilly and Company

Industry

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2030
Study completion
2030
First posted
Jul 2, 2025
Registry last updated
Jun 23, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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