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

A Phase 1a/1b Study of LY4052031, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Advanced or Metastatic Urothelial Carcinoma or Other Solid Tumors

Phase 1 Interventional Eli Lilly and Company · NCT06465069

This trial will test whether LY4052031 is safe and can help people with advanced or metastatic urothelial cancer or other solid tumors that express nectin‑4.

Quick facts

PhasePhase 1
Study typeInterventional
Enrollment420 (estimated)
Ages18 Years and up
SexAll
SponsorEli Lilly and Company Industry-sponsored
Drugs / interventionsenfortumab
Locations31 sites (Duarte, California and 30 other locations)
Trial IDNCT06465069 on ClinicalTrials.gov

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.

Who should consider this trial

Good fit: Ideal candidates are adults with advanced or metastatic solid tumors known to express nectin‑4—particularly urothelial carcinoma or certain triple‑negative breast cancers—who have received prior standard therapies when applicable or have no standard options and meet other health criteria.

Not a fit: Patients whose tumors do not express nectin‑4, those with early‑stage disease who have curative standard options, or those with significant organ dysfunction or contraindications to an antibody‑drug conjugate are unlikely to benefit from this trial.

Why it matters

Potential benefit: If successful, LY4052031 could become an additional treatment option that targets nectin‑4–positive tumors and potentially shrinks tumors or controls disease with an acceptable safety profile.

How similar studies have performed: A similar nectin‑4–targeting antibody‑drug conjugate (enfortumab vedotin) has shown clinical benefit in urothelial cancer, so the general approach has proven activity although LY4052031 is a different investigational agent.

Eligibility criteria

Show full inclusion / exclusion criteria 
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/B1/B2: 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.
* Prior enfortumab vedotin specific requirements:

  * Cohorts A1/A2/C: 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 when receiving enfortumab vedotin
* Individuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention

Where this trial is running

Duarte, California and 30 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
View on ClinicalTrials.gov → Find more trials like this →
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Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.