A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors

About

Brief Summary

The purpose of this study is to find out whether the study drug, LY4052031, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors including urothelial cancer. The study is conducted in two parts - phase Ia (dose-escalation, dose-optimization) and phase Ib (dose-expansion). The study will last up to approximately 4 years.

Primary Purpose

Treatment

Study Type

Interventional

Phase

Phase 1

Eligibility

Gender

All

Healthy Volunteers

Minimum Age

18 Years

Maximum Age

N/A

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