A Study Of LY4052031 In Participants With Advanced Or Metastatic Urothelial Cancer Or Other Solid Tumors

Study Overview

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

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.

This is a Phase 1a/1b multicenter, open-label study in participants with advanced or metastatic solid tumor malignancies known to express Nectin 4. This study evaluates an antibody-drug conjugate that binds to the protein nectin-4, which is expressed on certain cancer cells, delivering the drug to the cancer. This study is comprised of two phases: Dose Escalation and Dose Optimization (1a), and Dose expansion (1b). Phase 1a will assess the safety, tolerability, and pharmacokinetics of LY4052031 to determine the recommended phase 2 dose (RP2D)/optimal dose. Phase 1b will evaluate efficacy and safety of LY4052031 at the RP2D/optimal dose in expansion cohorts based on tumor type and/or treatment history.

Metastatic Solid Tumor
Recurrent Solid Tumor
Advanced Solid Tumor
Urinary Bladder Neoplasm
Triple Negative Breast Cancer
Non-small Cell Lung Cancer
Esophageal Cancer
Pancreatic Cancer
Ovarian Cancer
Cervical Cancer
Head and Neck Squamous Cell Carcinoma
Prostate Cancer
Renal Pelvis Cancer
Bladder Cancer

DRUG: LY4052031

18882
2024-512927-36-00 (CTIS Identifier) (CTIS: )
J5I-OX-JZYA (OTHER Identifier) (OTHER: Eli Lilly and Company)
LOXO-LNC-24001 (OTHER Identifier) (OTHER: Eli Lilly and Company)

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2024-06-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2025-08-15
First Submitted that Met QC Criteria 2024-06-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ACTUAL) 2025-08-20
First Posted (ACTUAL) 2024-06-18	Results First Posted N/A	Last Verified 2025-06

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Non Randomized

Interventional Model:
Parallel

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment
EXPERIMENTAL: LY4052031 (Dose-escalation, Cohort A1) Escalating doses of LY4052031 administered intravenously (IV).	DRUG: LY4052031 Intravenous
EXPERIMENTAL: LY4052031 (Dose-optimization, Cohort A2) Comparing 2 or more doses (evaluated during dose escalation) of LY4052031 administered IV.	DRUG: LY4052031 Intravenous
EXPERIMENTAL: LY4052031 (Dose-expansion, Cohort B1, B2, C1) LY4052031 administered IV.	DRUG: LY4052031 Intravenous

Participant Group/Arm

Intervention/Treatment

EXPERIMENTAL: LY4052031 (Dose-escalation, Cohort A1)

Escalating doses of LY4052031 administered intravenously (IV).

DRUG: LY4052031

Intravenous

EXPERIMENTAL: LY4052031 (Dose-optimization, Cohort A2)

Comparing 2 or more doses (evaluated during dose escalation) of LY4052031 administered IV.

DRUG: LY4052031

Intravenous

EXPERIMENTAL: LY4052031 (Dose-expansion, Cohort B1, B2, C1)

LY4052031 administered IV.

DRUG: LY4052031

Intravenous

Primary Outcome Measures	Measure Description	Time Frame
Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031	Number of participants with dose-limiting toxicities (DLTs)	Cycle 1 (21 Days)
Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR)	ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)	Up to Approximately 48 Months or 4 Years

Secondary Outcome Measures	Measure Description	Time Frame
To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)	PK: Cmin of LY4052031	Cycle 1 (21 Days)
To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)	PK: AUC of LY4052031	Cycle 1 (21 Days)
To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)	ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1))	Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR)	DOR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)	TTR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)	PFS per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)	DCR per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)	OS per investigator assessed RECIST 1.1	Up to Approximately 48 Months or 4 Years

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Name: There may be multiple sites in this clinical trial. 1-877-CTLILLY (1-877-285-4559) or

Phone Number: 13176154559

Email: clinical_inquiry_hub@lilly.com

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person’s general health condition or prior treatments.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

STUDY_DIRECTOR: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 9 AM - 5 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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