A Phase Ia/Ib Study of LY4052031, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Advanced or Metastatic Urothelial Carcinoma or Other Solid Tumors

Study Identifier:
LOXO-LNC-24001 (J5I-OX-JZYA)
CT.gov Identifier:
NCT06465069
EudraCT Identifier:
202451000000
EU Trial (CTIS) Number:
2024-512927-36-00
Study Contact Information:
(210) 593-5651 or [email protected]
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Study 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. To study LY4052031 in patients (pts) with advanced or metastatic UC or other solid tumors known to express nectin-4. Nectin-4 expression and other biomarker data will be generated and correlated with clinical activity.

Phase 1a Dose escalation and optimization: Determining the RP2D/optimal dose of LY4052031 in subjects with selected advanced malignancies. Phase 1b Dose extension: Evaluating the antitumor activity of LY4052031 in subjects with selected advanced malignancies.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Solid Tumor
  • Bladder
  • Breast Cancers
  • Non-Small Cell Lung Cancer
  • Esophageal
  • Pancreas
  • Ovarian
  • Cervical cancer
  • Head & Neck
  • Prostate
  • Renal
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I
    Sex
    Female & Male
    Age
    18+ years
    Study Drug
  • Drug: Experimental: LY4052031 (Dose-escalation, Cohort A1)
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  • Drug: Experimental: LY4052031 (Dose-optimization, Cohort A2)
  • Drug: Experimental: LY4052031 (Dose-expansion, Cohort B1, B2, C1)
  • Drug: EORTC-NCI-AACR 2024:
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruiting

    Requirements information
    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
    • Eligible pts have ECOG PS 0–1 with a histologic diagnosis of advanced UC, triple-negative breast, nonsmall cell lung, esophageal, pancreatic, gastric (Japan only), ovarian, cervical, head and neck squamous cell carcinoma, or prostate cancer.
    • Pts must have progressed on or be ineligible for all available standard therapies, with no limit on the number of prior therapies.
    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
    • Pts must have progressed on or be ineligible for all available standard therapies, with no limit on the number of prior therapies.

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Midwest
    Grand Rapids, MI, United States, 49546
    Investigator
    Nehal Lakhani
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Bladder
    Breast Cancers
    Non-Small Cell Lung Cancer
    Esophageal
    Pancreas
    Ovarian
    Cervical cancer
    Head & Neck
    Prostate
    Renal
    Location
    START San Antonio
    San Antonio, TX, United States, 78229
    Investigator
    Amita Patnaik
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Bladder
    Breast Cancers
    Non-Small Cell Lung Cancer
    Esophageal
    Pancreas
    Ovarian
    Cervical cancer
    Head & Neck
    Prostate
    Renal
    Location
    START Mountain Region
    West Valley City, UT, United States, 84119
    Investigator
    Justin Call
    Status
    Recruiting
    Condition(s) Treated at Site
    Solid Tumor
    Bladder
    Breast Cancers
    Non-Small Cell Lung Cancer
    Esophageal
    Pancreas
    Ovarian
    Cervical cancer
    Head & Neck
    Prostate
    Renal
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Irene Moreno
    Status
    Recruitment on Hold
    Condition(s) Treated at Site
    Solid Tumor
    Bladder
    Breast Cancers
    Non-Small Cell Lung Cancer
    Esophageal
    Pancreas
    Ovarian
    Cervical cancer
    Head & Neck
    Prostate
    Renal