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No longer recruiting (closed or complete)Last updated: 20 March 2026

Nectin-2 ADC: This study will evaluate whether a new drug (LY4101174) is safe, tolerable and effective in people with advanced or metastatic solid cancersA Phase 1 Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors

Trial purpose

Medical clipboardCancer treatment

Tumor type

Multi-Cancer Multi-Cancer

Age

People18+

Trial acronym

Nectin-2 ADC

Clinical summary

Summary

This study is recruiting people with one of the following solid tumour cancers, that are known to express Nectin 4:

  • Urothelial carcinoma
  • Triple-negative breast cancer
  • Non-small cell lung cancer
  • Oesophageal cancer
  • Pancreatic cancer
  • Ovarian cancer
  • Cervical cancer (squamous cell carcinoma)
  • Head and neck squamous cell carcinoma
  • Prostate cancer

This study is comprised of two phases: Dose Escalation and Dose Optimisation (1a), and Dose expansion (1b).

Phase 1a will assess the safety and tolerability of LY4101174, as well as how LY4101174 works in the body, to determine the recommended dose.

Phase 1b will evaluate effectiveness and safety of LY4101174 at the recommended dose (established in Phase 1a) in seven randomally allocated cohorts based on tumour type and/or treatment history. 

LY4101174 will be administered via IV infusion.

Conditions

This trial is treating people with advanced or metastatic solid tumours

Eligibility

Inclusion

  • 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

Exclusion

  • 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 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

Inclusion

  • You have had treatment, but your cancer has come back (relapsed or recurrent).
  • Your cancer has spread to other parts of the body (metastatic) or has grown into nearby parts of the body (locally advanced).
  • Your cancer has not spread to other parts of the body (localised).
  • You have been diagnosed with cancer, but have not received any treatment.
  • You have had treatment but your cancer has gotten worse or has not responded to the treatment you have been given.

Exclusion

  • You have been diagnosed with a prior or secondary type of cancer.
  • You have certain types of non-cancer medical conditions.
Message

Clinical trials have complex eligibility criteria, and other criteria may apply for this trial. Ask your doctor about whether this trial could be right for you.

Participating hospitals

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More information

Trial Identifiers

Information on this page is partially produced from ClinicalTrials.gov *. View further details about this trial on the registry via the links below:

  • NCT06238479 *
  • LOXO-ENC-23001; J5A-OX-JZWA; 2023-509867-26-00

Trial sponsor

Eli Lilly and Company

Scientific Title

A Phase 1 Trial Investigating LY4101174, an Antibody-Drug Conjugate Targeting Nectin-4, in Participants With Recurrent, Advanced or Metastatic Solid Tumors

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