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

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

NCT ID: NCT06465069

Condition: 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

Conditions: Official terms:
Carcinoma
Neoplasms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Squamous Cell
Urinary Bladder Neoplasms
Triple Negative Breast Neoplasms
Squamous Cell Carcinoma of Head and Neck
Pelvic Neoplasms

Conditions: Keywords:
Bladder Cancer
Bladder Neoplasm
Bladder Urothelial Carcinoma
Urinary Bladder Cancer
Urinary Tract Cancer
Urothelial Neoplasms
Renal Pelvis Cancer
Ureter Cancer
Nectin-4
Antibody Drug Conjugate (ADC)
Triple Negative Breast Cancer (TNBC)
Non-small Cell Lung Cancer (NSCLC)
Head and Neck Squamous Cell Carcinoma (HNSCC)

Study type: Interventional

Study phase: Phase 1

Overall status: Recruiting

Study design:

Allocation: Non-Randomized

Intervention model: Parallel Assignment

Primary purpose: Treatment

Masking: None (Open Label)

Intervention:

Intervention type: Drug
Intervention name: LY4052031
Description: Intravenous
Arm group label: LY4052031 (Dose-escalation, Cohort A1)
Arm group label: LY4052031 (Dose-expansion, Cohort B1, B2, C1)
Arm group label: LY4052031 (Dose-optimization, Cohort A2)

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 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.

Criteria for 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, 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) - Cohorts A2, B1, B2, C: measurable disease required 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 or 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

Gender: All

Minimum age: 18 Years

Maximum age: N/A

Healthy volunteers: No

Locations:

Facility:
Name: Massachusetts General Hospital

Address:
City: Boston
Zip: 02114
Country: United States

Status: Recruiting

Facility:
Name: START Midwest

Address:
City: Grand Rapids
Zip: 49546
Country: United States

Status: Recruiting

Facility:
Name: Icahn School of Medicine at Mount Sinai

Address:
City: New York
Zip: 10029
Country: United States

Status: Recruiting

Facility:
Name: Columbia University Irving Medical Center

Address:
City: New York
Zip: 10032
Country: United States

Status: Recruiting

Facility:
Name: South Texas Accelerated Research Therapeutics (START)

Address:
City: San Antonio
Zip: 78229-3307
Country: United States

Status: Recruiting

Facility:
Name: START Mountain Region

Address:
City: West Valley City
Zip: 84119
Country: United States

Status: Recruiting

Facility:
Name: START Madrid-CIOCC

Address:
City: Madrid
Zip: 28050
Country: Spain

Status: Recruiting

Start date: July 1, 2024

Completion date: May 2027

Lead sponsor:
Agency: Eli Lilly and Company
Agency class: Industry

Source: Eli Lilly and Company

Record processing date: ClinicalTrials.gov processed this data on November 12, 2024

Source: ClinicalTrials.gov page: https://clinicaltrials.gov/ct2/show/NCT06465069
https://trials.lilly.com/en-US/trial/503555