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A Study of LY4052031 in Participants With Advanced or Metastatic Urothelial Cancer or Other Solid Tumors
NCT06465069 · Eli Lilly and Company
In plain English
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Official title
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
About this study
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
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
Study design
Enrollment target: 420 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2024-07-01
Estimated completion: 2027-05
Last updated: 2026-03-24
Interventions
Drug: LY4052031
Primary outcomes
- • Phase 1a: To determine the recommended phase 2 dose (RP2D) optimal dose(s) of LY4052031 (Cycle 1 (21 Days))
- • Phase 1b: To assess the antitumor activity of LY4052031 Monotherapy: Overall response rate (ORR) (Up to Approximately 48 Months or 4 Years)
Sponsor
Eli Lilly and Company · industry
Contacts & investigators
ContactTrial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or · contact · LillyTrials@Lilly.com · 1-317-615-4559
ContactPhysicians interested in becoming principal investigators please contact · contact · clinical_inquiry_hub@lilly.com
InvestigatorCall 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST) · study_director, Eli Lilly and Company
All locations (28)
City of Hope National Medical CenterRecruiting
Duarte, California, United States
Sarah Cannon Research Institute at HealthOneRecruiting
Denver, Colorado, United States
Florida Cancer Specialists and Research InstituteRecruiting
St. Petersburg, Florida, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
START Midwest Cancer and Hematology Centers of W MichiganRecruiting
Grand Rapids, Michigan, United States
Washington University School of Medicine in St. LouisRecruiting
St Louis, Missouri, United States
Icahn School of Medicine at Mount SinaiRecruiting
New York, New York, United States
Columbia University Irving Medical CenterRecruiting
New York, New York, United States
Memorial Sloan Kettering Cancer CenterRecruiting
New York, New York, United States
Sarah Cannon Research InstituteRecruiting
Nashville, Tennessee, United States
University of Texas MD Anderson Cancer CenterRecruiting
Houston, Texas, United States
South Texas Accelerated Research Therapeutics (START)Recruiting
San Antonio, Texas, United States
START Mountain RegionRecruiting
West Valley City, Utah, United States
St Vincent's HospitalRecruiting
Darlinghurst, Australia
Linear Clinical ResearchRecruiting
Nedlands, Australia
Beijing Cancer hospitalNot Yet Recruiting
Beijing, China
Sun Yat-sen University Cancer CenterNot Yet Recruiting
Guangzhou, China
Renji Hospital, Shanghai Jiaotong University School of MedicineNot Yet Recruiting
Shanghai, China
Institut Gustave Roussy (Igr)Recruiting
Villejuif, France
National Cancer Center Hospital EastRecruiting
Kashiwa, Chiba, Japan
Aichi Cancer Center HospitalRecruiting
Nagoya, Japan
Asan Medical CenterRecruiting
Seoul, South Korea
Catalan Institute of Oncology Duran i Reynals HospitalRecruiting
Barcelona, Spain
Hospital Universitario 12 de OctubreRecruiting
Madrid, Spain
Hospital Madrid Norte SanchinarroRecruiting
Madrid, Spain
Hospital Universitario Virgen Del RocioRecruiting
Seville, Spain
St Bartholomew's HospitalRecruiting
London, United Kingdom
The Christie NHS Foundation TrustRecruiting
Manchester, United Kingdom