A Study of LY4175408 in Participants With Advanced Cancer

NCT07046923RecruitingPHASE1INTERVENTIONAL

Summary

Key Facts

Lead Sponsor

Eli Lilly and Company

Enrollment

240

Start Date

2025-07-28

Completion Date

2030-07-01

Study Type

INTERVENTIONAL

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

Interventions

LY4175408

Conditions

CarcinomaNon-Small-Cell LungSmall Cell Lung CarcinomaEndometrial NeoplasmsNeoplasm MetastasisTriple Negative Breast Cancer

Eligibility

Age Range

18 Years+

Sex

ALL

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; 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 ≤1.
* For dose optimization/dose and expansion cohorts (Cohort A2, Cohort B): Measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

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).
* 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.

Outcome Measures

Primary Outcomes

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 Outcomes

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

Per investigator assessed RECIST 1.1

Time frame: Baseline up to approximately 4 years

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

Per investigator assessed RECIST 1.1

Time frame: Baseline up to approximately 4 years

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

Per investigator assessed RECIST 1.1

Time frame: Baseline up to approximately 4 years

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

Per investigator assessed RECIST 1.1

Time frame: Baseline up to approximately 4 years

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

Per investigator assessed RECIST 1.1

Time frame: Baseline up to approximately 4 years

Locations

Stanford Cancer Center, Stanford, United States

Florida Cancer Specialists - Lake Nona - Sarah Cannon Research Institute, Orlando, United States

Florida Cancer Specialists - Sarasota, Sarasota, United States

The University of Chicago Medical Center (UCMC), Chicago, United States

Community Health Network, Indianapolis, United States

Massachusetts General Hospital, Boston, United States

Washington University, St Louis, United States

John Theurer Cancer Center At Hackensack UMC, Hackensack, United States

Columbia University, New York, United States

David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center, New York, United States

The Ohio State University (OSU) Wexner Medical Center, Columbus, United States

Sarah Cannon Research Institute, Nashville, United States

MD Anderson Cancer Center, Houston, United States

START Mountain Region, West Valley City, United States

NEXT Virginia, Fairfax, United States

Centre Leon Berard, Lyon, France

Institut Gustave Roussy, Villejuif, France

Kyoto University Hospital, Kyoto, Japan

National Cancer Center Hospital, Tokyo, Japan

Cancer Institute Hospital of JFCR, Tokyo, Japan

Severance Hospital, Yonsei University Health System, Seoul, South Korea

Samsung Medical Center, Seoul, South Korea

Hospital Universitario Vall d'Hebron, Barcelona, Spain

Hospital Universitario 12 de Octubre, Madrid, Spain

A Study of LY4175408 in Participants With Advanced Cancer