A Study of LY4175408 in Participants With Advanced Cancer

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

Overview

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.

Interventions

• Drug LY4175408
  IV infusion
• Drug Pembrolizumab
  IV infusion
• Drug Carboplatin
  IV infusion
• Drug Cisplatin
  IV infusion

Primary outcome measures

• 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]

Secondary outcome measures (7)

• 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

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Sequential

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 15 centers

• Stanford Medicine Cancer Center — Stanford
• Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute — Orlando
• Florida Cancer Specialists - Sarasota — Sarasota
• The University of Chicago Medical Center (UCMC) — Chicago
• Community Health Network — Indianapolis
• Massachusetts General Hospital — Boston
• Washington University — St Louis
• John Theurer Cancer Center At Hackensack UMC — Hackensack
• … and 7 more centers

China · 3 centers

• West China Hospital, Sichuan University — Chengdu
• Shanghai East Hospital, Tongji University — Shanghai
• Tongji Hospital - Tongji Medical College of HUST — Wuhan

Japan · 3 centers

• Kyoto University Hospital — Kyoto
• National Cancer Center Hospital — Tokyo
• Cancer Institute Hospital of JFCR — Tokyo

France · 2 centers

• Centre Leon Berard — Lyon
• Institut Gustave Roussy — Villejuif

South Korea · 2 centers

• Severance Hospital, Yonsei University Health System — Seoul
• Samsung Medical Center — Seoul

Spain · 2 centers

• Hospital Universitario Vall d'Hebron — Barcelona
• Hospital Universitario 12 de Octubre — Madrid

Identifiers

NCT: NCT07046923 · 27401 · J6D-MC-JSDA · 2025-521916-20-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗