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
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.
Arms & interventions
- DrugLY4052031
Intravenous
Outcome measures
Primary
Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031
Number of participants with dose-limiting toxicities (DLTs)
Time frame: 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)
Time frame: Up to Approximately 48 Months or 4 Years
Secondary
To characterize the pharmacokinetics (PK) properties of LY4052031: Minimum Plasma Concentration (Cmin)
Time frame: Cycle 1 (21 Days)
To characterize the PK properties of LY4052031: Area under the concentration versus time curve (AUC)
Time frame: Cycle 1 (21 Days)
To evaluate the preliminary antitumor activity of LY4052031: Overall response rate (ORR)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Duration of response (DOR)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Time to response (TTR)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Progression free survival (PFS)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Disease control rate (DCR)
Time frame: Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4052031: Overall survival (OS)
Time frame: Up to Approximately 48 Months or 4 Years
Eligibility criteria
Study locations (17)
City of Hope National Medical Center
Duarte, California, 91010-0269
UCLA Department of Medicine-Hematology/Oncology
Los Angeles, California, 90024
Sarah Cannon Research Institute at HealthOne
Denver, Colorado, 80218
Florida Cancer Specialists and Research Institute
St. Petersburg, Florida, 33705
University of Chicago Hospital
Chicago, Illinois, 60637
IU Simon Cancer Center
Indianapolis, Indiana, 46202
Massachusetts General Hospital
Boston, Massachusetts, 02215
START Midwest Cancer and Hematology Centers of W Michigan
Grand Rapids, Michigan, 49546
Washington University School of Medicine in St. Louis
St Louis, Missouri, 63110
Icahn School of Medicine at Mount Sinai
New York, New York, 10029-6574
Columbia University Irving Medical Center
New York, New York, 10032-3729
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
Sarah Cannon Research Institute
Nashville, Tennessee, 37203
University of Texas MD Anderson Cancer Center
Houston, Texas, 77030-4000
South Texas Accelerated Research Therapeutics (START)
San Antonio, Texas, 78229
University of Utah - Huntsman Cancer Institute
Salt Lake City, Utah, 84112
START Mountain Region
West Valley City, Utah, 84119