A Phase I Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors

Study Identifier:
LOXO-ENC-23001
CT.gov Identifier:
NCT06238479
EudraCT Identifier:
202351000000
EU Trial (CTIS) Number:
2023-509867-26-00
Study Contact Information:
(210) 593-5651 or [email protected]
Terminated/Withdrawn

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Study Summary

The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with advanced, or metastatic solid tumors. 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.

The study will be conducted in 2 phases: phase 1a dose escalation/dose optimization and phase 1b dose expansion. Dose escalation will utilize a Bayesian optimal interval design. Additional pts will be allowed to backfill to previously cleared dose levels that demonstrate therapeutically relevant exposures or direct evidence of clinical activity. The dose-limiting toxicity evaluation period will be 21 or 28 days based on dosing schedules. Phase 1b dose expansion cohorts will enroll pts with selected tumor types: mUC with no prior EV treatment (cohort B1), mUC with prior EV treatment (cohort B2), and other selected non-UC tumors (cohort C).

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: LY4101174 (Dose-escalation, Cohort A1)
    • Read More
  • Drug: Experimental: LY4101174 (Dose-optimization, Cohort A2)
  • Drug: Experimental: LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5)
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Terminated/Withdrawn

    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 C1: triple negative breast cancer
    • - Cohort C2: non-small cell lung cancer
    • - Cohort C3: ovarian or fallopian tube cancer
    • - Cohort C4: cervical cancer
    • - Cohort C5: head and neck squamous cell carcinoma
    • - Prior Systemic Therapy Criteria:
    • - Cohort A1/C1-5: 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/C1-5: 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, C1-5: 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
    • 1 Patients with one of the following solid tumors: 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 C1: Triple-negative breast cancer Cohort C2: Non-small cell lung cancer Cohort C3: Ovarian or fallopian tube cancer Cohort C4: Cervical cancer Cohort C5: Head and neck squamous cell carcinoma
    • 2 Previous systemic treatment criteria: Cohort A1/C1-5: Subjects who have received all standard treatments and are considered suitable candidates by the treating investigator; or there is no standard treatment available for the disease. There is no limit on the number of previous treatment lines received. Cohort A2/B1/B2: Subjects must have previously received at least one treatment regimen for advanced or metastatic disease. There is no limit on the number of previous treatment lines received.
    • 3 Specific requirements for prior enfortumab vedotin treatment: Cohorts A1/A2/C1-5: Prior treatment with enfortumab vedotin is permitted but not required. Cohort B1: Subjects must not have received prior enfortumab vedotin treatment for metastatic/advanced disease. Cohort B2: Subjects must have received prior enfortumab vedotin treatment for advanced/metastatic disease.
    • 4 Measurability of lesions Cohort A1: Measurable or non-measurable disease according to RECIST 1.1 Cohorts A2, B1, B2, C1-5: Measurable disease according to RECIST v1.1
    • 5 Eastern Cooperative Oncology Group (ECOG) performance status score was 0 or 1.
    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 history of corneal transplant
    • Any serious unresolved toxicities from prior therapy
    • Significant cardiovascular disease
    • Current of history of intestinal obstruction in the previous 3 months
    • Recent thromboembolic event and/or clinically significant bleeding
    • 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
    • Individual with active uncontrolled infection

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    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