A Study of LY4175408 in Participants With Advanced Cancer

NCT07046923
clinicaltrials.gov
Phase
Phase 1
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Recruitment status
Recruiting
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Participants
240
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Lead sponsor
Eli Lilly and Company
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Start date
2025-07-28
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Number of sites
27
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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.
clinicaltrials.gov
Short title
A Study of LY4175408 in Participants With Advanced Cancer
clinicaltrials.gov
Official 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
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Control arm
Open label
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Registry reports results
No
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Listing at source
Listed
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Recruitment status
Recruiting
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Phase
Phase 1
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Study type
Interventional
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Completion date
2030-07-01
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First posted
2025-07-02
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Registry last updated
2026-06-23
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Primary completion date
2030-07-01
clinicaltrials.gov
Start date
2025-07-28
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Participants
240
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Participant count basis
Estimated
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Planned participants
240
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Protocol amendments
2
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Number of sites
27
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Data monitoring committee
Yes
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Registry sponsor category
Industry
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Lead sponsor
Eli Lilly and Company
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Source registry
ClinicalTrials.gov
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Registry ID
NCT07046923
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ClinicalTrials.gov ID
NCT07046923
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Registry record
Open registry record
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Allocation
Not randomised
Model
Sequential
Purpose
Treatment
Masking
No masking
Sources for study design
clinicaltrials.gov

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

    Timeframe: 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)

    Timeframe: Baseline up to approximately 4 years

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

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

    Timeframe: 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)

    Timeframe: First 4 cycles (84 days)

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

    Timeframe: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Timeframe: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Timeframe: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Timeframe: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

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

    Timeframe: Baseline up to approximately 4 years

    Per investigator assessed RECIST 1.1

Sources for outcomes
clinicaltrials.gov

Sex
All
Age groups
Adults, Older adults
Minimum age
18 Years
Healthy volunteers
No

  • 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

  • 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.
Sources for eligibility
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  • Stanford Medicine Cancer CenterStanford, United StatesRecruiting
  • Florida Cancer Specialists - Lake Nona - Sarah Cannon Research InstituteOrlando, United StatesRecruiting
  • Florida Cancer Specialists - SarasotaSarasota, United StatesRecruiting
  • The University of Chicago Medical Center (UCMC)Chicago, United StatesRecruiting
  • Community Health NetworkIndianapolis, United StatesRecruiting
  • Massachusetts General HospitalBoston, United StatesRecruiting
  • Washington UniversitySt Louis, United StatesRecruiting
  • John Theurer Cancer Center At Hackensack UMCHackensack, United StatesRecruiting
  • Columbia UniversityNew York, United StatesRecruiting
  • David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer CenterNew York, United StatesRecruiting
  • The Ohio State University (OSU) Wexner Medical CenterColumbus, United StatesRecruiting
  • Sarah Cannon Research InstituteNashville, United StatesRecruiting
  • MD Anderson Cancer CenterHouston, United StatesRecruiting
  • START Mountain RegionWest Valley City, United StatesRecruiting
  • NEXT VirginiaFairfax, United StatesRecruiting
  • West China Hospital, Sichuan UniversityChengdu, ChinaNot yet recruiting
  • Shanghai East Hospital, Tongji UniversityShanghai, ChinaNot yet recruiting
  • Tongji Hospital - Tongji Medical College of HUSTWuhan, ChinaNot yet recruiting
  • Centre Leon BerardLyon, FranceRecruiting
  • Institut Gustave RoussyVillejuif, FranceRecruiting
  • Kyoto University HospitalKyoto, JapanRecruiting
  • National Cancer Center HospitalTokyo, JapanRecruiting
  • Cancer Institute Hospital of JFCRTokyo, JapanRecruiting
  • Severance Hospital, Yonsei University Health SystemSeoul, South KoreaRecruiting
  • Samsung Medical CenterSeoul, South KoreaRecruiting

And 2 more, listed on the interactive page.

Sources for sites
clinicaltrials.gov

  • 2025
  • 2025-521916-20-00
  • J6D-MC-JSDA
Sources for references
clinicaltrials.gov

Related records

Drugs (3)

Lead sponsors (1)

Conditions (4)

Targets (1)