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NCT06465069PHASE1Recruiting

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

Eli Lilly and Company

Start Date

7/1/2024

Completion Date

5/1/2027

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.

Detailed Description

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.

Eligibility Criteria

Age Range: 18 years to No maximum

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

Interventions

DRUG

LY4052031

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Conditions

Metastatic Solid TumorRecurrent Solid TumorAdvanced Solid TumorUrinary Bladder NeoplasmTriple Negative Breast CancerNon-small Cell Lung CancerEsophageal CancerPancreatic CancerOvarian CancerCervical CancerHead and Neck Squamous Cell CarcinomaProstate CancerRenal Pelvis CancerBladder Cancer

Locations

City of Hope National Medical Center

Duarte, California 91010-0269

United States

University of California, San Diego (UCSD) - Moores Cancer Center

La Jolla, California 92093

United States

UCLA Department of Medicine-Hematology/Oncology

Los Angeles, California 90024

United States

Sarah Cannon Research Institute at HealthOne

Denver, Colorado 80218

United States

Florida Cancer Specialists and Research Institute

St. Petersburg, Florida 33705

United States

University of Chicago Hospital

Chicago, Illinois 60637

United States

IU Simon Cancer Center

Indianapolis, Indiana 46202

United States

Massachusetts General Hospital

Boston, Massachusetts 02215

United States

START Midwest Cancer and Hematology Centers of W Michigan

Grand Rapids, Michigan 49546

United States

Washington University School of Medicine in St. Louis

St Louis, Missouri 63110

United States

NYU Langone Medical Center - Perlmutter Cancer Center (NYU Cancer Institute)

New York, New York 10016

United States

Icahn School of Medicine at Mount Sinai

New York, New York 10029-6574

United States

Columbia University Irving Medical Center

New York, New York 10032-3729

United States

Memorial Sloan Kettering Cancer Center

New York, New York 10065

United States

University Hospitals Cleveland Medical Center

Cleveland, Ohio 44106

United States

Sarah Cannon Research Institute

Nashville, Tennessee 37203

United States

Tennessee Oncology PLLC

Nashville, Tennessee 37203

United States

University of Texas MD Anderson Cancer Center

Houston, Texas 77030-4000

United States

South Texas Accelerated Research Therapeutics (START)

San Antonio, Texas 78229

United States

University of Utah - Huntsman Cancer Institute

Salt Lake City, Utah 84112

United States

START Mountain Region

West Valley City, Utah 84119

United States

St Vincent's Hospital

Darlinghurst, 2010

Australia

Linear Clinical Research

Nedlands, 6009

Australia

Beijing Cancer hospital

Beijing, 100142

China

Sun Yat-sen University Cancer Center

Guangzhou, 510060

China

Renji Hospital, Shanghai Jiaotong University School of Medicine

Shanghai, 200000

China

Institut Gustave Roussy (Igr)

Villejuif, 94805

France

National Cancer Center Hospital

Chūōku, 104-0045

Japan

National Cancer Center Hospital East

Kashiwa, Chiba, 277-8577

Japan

The Cancer Institute Hospital of JFCR

Kōtō City, 135-8550

Japan

Aichi Cancer Center Hospital

Nagoya, 464-8681

Japan

Asan Medical Center

Seoul, 05505

South Korea

Catalan Institute of Oncology Duran i Reynals Hospital

Barcelona, 8908

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Hospital Madrid Norte Sanchinarro

Madrid, 28050

Spain

Hospital Universitario Virgen Del Rocio

Seville, 41013

Spain

St Bartholomew's Hospital

London, EC1A 7BE

United Kingdom

The Christie NHS Foundation Trust

Manchester, M20 4BX

United Kingdom