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:
EudraCT Identifier:
EU Trial (CTIS) Number:
Study Contact Information:
Recruiting
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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.
Bladder
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Prostate
Renal
Gastric
Head & Neck
Digestive & Intestinal
Cervical cancer
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.
Phase I
Sex
Female & Male
Age
18+ years
Study Drug
Drug: Experimental: LY4052031 (Dose-escalation, Cohort A1)
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Drug: EORTC-NCI-AACR 2024: LY4052031 is administered intravenously once every 3 weeks. The study consists of phase 1a dose escalation/dose optimization and phase 1b dose expansion. Dose escalation will utilize a Bayesian optimal interval design. Additional pts will backfill previously cleared dose levels that demonstrate therapeutically relevant exposures or direct evidence of clinical activity. Optional dose optimization will involve randomized evaluation of 2 or more dose levels selected in the dose escalation phase. Dose expansion will enroll pts with UC who are EV-naive (cohort B1) and with prior EV treatment (cohort B2), or with non-UC solid tumors (cohort C).
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 cancerCohort A2/B/D: urothelial carcinomaCohort 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 cancerPrior 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 therapiesCohort 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.Cohort D: Treatment-naive for locally advanced or metastatic urothelial cancer.Prior enfortumab vedotin specific requirements:Cohorts A1/A2/C/D: prior treatment with enfortumab vedotin is allowed, but not requiredCohort B1: individual must be enfortumab vedotin naive in the advanced/metastatic settingCohort B2: individual must have received enfortumab vedotin in the metastatic/advanced setting.Measurability of diseaseCohort 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 v1.1Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1Have 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 metastasesIndividual with uncontrolled hypercalcemiaIndividual with uncontrolled diabetesIndividual with evidence of corneal keratopathy or keratitis, and history of corneal transplantAny serious unresolved toxicities from prior therapySignificant cardiovascular diseaseRecent thromboembolic event and/or clinically significant bleeding disorderProlongation of QT interval corrected for heart rate using Fridericia's formula (QTcF) ≥ 470 msHistory of pneumonitis/interstitial lung diseaseHistory of Grade ≥3 skin toxicity associated with enfortumab vedotin that required treatment discontinuationIndividuals who are pregnant, breastfeeding or plan to breastfeed during study or within 30 days of last dose of study intervention
Clinical Study Information for Healthcare Providers
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Study Locations
Location
Investigator
Status
Condition(s) Treated at Site
Location
START Mountain Region
West Valley City, UT, United States, 84119
Investigator
Justin Call
Status
Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Prostate
Renal
Gastric
Head & Neck
Digestive & Intestinal
Cervical cancer
Location
START Madrid, Spain (CIOCC)
Madrid, Spain, 28050
Investigator
Irene Moreno
Status
Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Prostate
Renal
Gastric
Head & Neck
Digestive & Intestinal
Cervical cancer
Location
START Midwest
Grand Rapids, MI, United States, 49546
Investigator
Nehal Lakhani
Status
Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Prostate
Renal
Gastric
Head & Neck
Digestive & Intestinal
Cervical cancer
Location
START San Antonio
San Antonio, TX, United States, 78229
Investigator
Amita Patnaik
Status
Recruiting
Condition(s) Treated at Site
Bladder
Breast Cancers
Non-Small Cell Lung Cancer
Ovarian
Pancreas
Prostate
Renal
Gastric
Head & Neck
Digestive & Intestinal
Cervical cancer