LY4052031 for advanced or metastatic urothelial and other nectin‑4–expressing solid tumors

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This is a multicenter, open‑label Phase 1a/1b study of an antibody‑drug conjugate that binds nectin‑4 to deliver a cytotoxic payload directly to cancer cells. Phase 1a uses dose escalation and dose optimization to determine the recommended Phase 2 dose and to characterize safety and pharmacokinetics. Phase 1b enrolls expansion cohorts by tumor type and treatment history to gather preliminary evidence of activity and additional safety data at the selected dose. The study is expected to run up to approximately four years across several U.S. cancer centers.

Why it matters

Who can join: the full rules

Inclusion Criteria:

* Have one of the following solid tumor cancers:

  * Cohort A1: urothelial carcinoma, triple negative breast cancer, non-small cell lung cancer, esophageal cancer, pancreatic cancer, ovarian cancer, cervical cancer (squamous cell carcinoma), head and neck squamous cell carcinoma or prostate cancer
  * Cohort A2/B/D: urothelial carcinoma
  * Cohort C: triple negative breast cancer, non-small cell lung cancer, ovarian cancer, cervical cancer, HNSCC (head and neck squamous cell carcinoma), esophageal cancer, pancreatic cancer, or prostate cancer
* Prior Systemic Therapy Criteria:

  * Cohort A1/C: Individual has received all standard therapies for which the participant was deemed to be an appropriate candidate by the treating investigator; OR there is no standard therapy available for the disease. There is no restriction on number of prior therapies
  * Cohort A2/B1/B2: Individual must have received at least one prior regimen in the advanced or metastatic setting. There is no restriction on number of prior therapies.
  * Cohort D: Treatment-naive for locally advanced or metastatic urothelial cancer.
* Prior enfortumab vedotin specific requirements:

  * Cohorts A1/A2/C/D: prior treatment with enfortumab vedotin is allowed, but not required
  * Cohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic setting
  * Cohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.
* Measurability of disease

  * Cohort A1: measurable or non-measurable disease as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST 1.1)
  * Measurable disease is required as defined by Response Evaluation Criteria in Solid Tumors v1.1 (RECIST v1.1) for all Cohorts. Cohort A1 may permit non-measurable disease as defined by RECIST v1.1
* Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate archival tumor tissue sample available or undergo a screening biopsy if allowed per country specific regulations

Exclusion Criteria:

* Individual with known or suspected uncontrolled CNS metastases
* Individual with uncontrolled hypercalcemia
* Individual with uncontrolled diabetes
* Individual with evidence of corneal keratopathy or keratitis, and history of corneal transplant
* Any serious unresolved toxicities from prior therapy
* Significant cardiovascular disease
* Recent thromboembolic event and/or clinically significant bleeding disorder
* Prolongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 ms
* History of pneumonitis/interstitial lung disease
* History of Grade ≥3 skin toxicity associated with enfortumab vedotin that required treatment discontinuation
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention

Where it's running

• City of Hope National Medical Center
  Duarte, California, United States Recruiting
• University of California, San Diego (UCSD) - Moores Cancer Center
  La Jolla, California, United States Recruiting
• UCLA Department of Medicine-Hematology/Oncology
  Los Angeles, California, United States Recruiting
• Sarah Cannon Research Institute at HealthOne
  Denver, Colorado, United States Recruiting
• Emory University
  Atlanta, Georgia, United States Recruiting
• University of Chicago Hospital
  Chicago, Illinois, United States Recruiting

Study contacts

• Study coordinator: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
• Email: LillyTrials@Lilly.com
• Phone: 1-317-615-4559

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.