A Study of LY4101174 in Participants With Recurrent, Advanced or Metastatic Solid Tumors (EXCEED)

May 20, 2026 updated by: Eli Lilly and Company

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

The purpose of this study is to find out whether the study drug, LY4101174, is safe, tolerable and effective in participants with select advanced or metastatic solid tumors. The study is conducted in two parts - phase 1a (dose-escalation, dose-optimization) and phase 1b (dose-expansion). The study will last up to approximately 4 years. Eligible patients will have the option to continue taking study drug after the study is complete.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Active, not recruiting

Conditions

Conditions

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.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This is a Phase 1a/1b multicenter, open-label study in participants with select advanced or metastatic solid tumors. 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 LY4101174 to determine the recommended phase 2 dose (RP2D)/optimal dose. Phase 1b will evaluate efficacy and safety of LY4101174 at the RP2D/optimal dose in 7 expansion cohorts based on tumor type and/or treatment history. At the completion of the trial, participants will have the option to continue receiving study drug at the discretion of the study doctor.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
490

Phase

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 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.
  • Name: Trial questions or participation questions: 1-877-CTLILLY (1-877-285-4559) or
  • Phone Number: 1-317-615-4559
  • Email: LillyTrials@Lilly.com

Study Contact Backup

Study Locations

  • Australia
      • Heidelberg, Australia, 3084
        • Austin Health
      • Kurralta Park, Australia, 5037
        • Icon Cancer Centre Kurralta Park
  • Belgium
      • Anderlecht, Belgium, 1070
        • Institut Jules Bordet
  • China
      • Beijing, China, 100034
        • Peking University First Hospital
      • Changsha, China, 410013
        • Hunan Cancer Hospital
      • Shanghai, China, 200433
        • Shanghai East Hospital
  • France
      • Lille, France, 59020
        • Centre Oscar Lambret
      • Lyon, France, 69373
        • Centre Léon Bérard
      • Marseille, France, 13273
        • Institut Paoli-Calmettes
      • Strasbourg, France, 67098
        • CHU Strasbourg-Hautepierre
      • Villejuif, France, 94805
        • Gustave Roussy
  • Japan
      • Chūōku, Japan, 104-0045
        • National Cancer Center Hospital
      • Kashiwa, Japan, 277-8577
        • National Cancer Center Hospital East
      • Kyoto, Japan, 606-8507
        • Kyoto University Hospital
      • Kōtō City, Japan, 135-8550
        • The Cancer Institute Hospital of JFCR
  • Spain
      • Barcelona, Spain, 08035
        • Hospital Universitari Vall d'Hebron
      • Madrid, Spain, 28041
        • Hospital Universitario 12 de Octubre
      • Madrid, Spain, 28033
        • MD Anderson Cancer Center
      • Seville, Spain, 41013
        • Hospital Universitario Virgen del Rocío
  • United States
    • Florida
      • Orlando, Florida, United States, 32804
        • AdventHealth Orlando
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Emory University
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Massachusetts General Hospital
    • Missouri
      • St Louis, Missouri, United States, 63110
        • Washington University School of Medicine
    • New York
      • Mineola, New York, United States, 11501
        • Perlmutter Cancer Center at NYU Langone Hospital - Long Island
      • New York, New York, United States, 10065
        • Memorial Sloan Kettering Cancer Center
      • New York, New York, United States, 10016
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
    • Texas
      • Dallas, Texas, United States, 75390-8884
        • UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78229-3307
        • South Texas Accelerated Research Therapeutics (START)

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: LY4101174 (Dose-escalation, Cohort A1)
Escalating doses of LY4101174 administered intravenously (IV).
Drug: LY4101174
Intravenous
Experimental: LY4101174 (Dose-optimization, Cohort A2)
Comparing 2 or more doses (evaluated during dose escalation) of LY4101174 administered IV.
Drug: LY4101174
Intravenous
Experimental: LY4101174 (Dose-expansion, Cohort B1, B2, C1-C5)
LY4101174 administered IV.
Drug: LY4101174
Intravenous

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Phase 1a: To determine the recommended dose of LY4101174
Time Frame: First 2 Cycles (28 days)
Number of participants with dose-limiting toxicities (DLTs)
First 2 Cycles (28 days)
Phase 1a: To determine the recommended phase 2 dose (RP2D) or optimal dose of LY4101174
Time Frame: First 2 Cycles (28 days)
Number of participants with DLTs
First 2 Cycles (28 days)
Phase 1b: To assess the antitumor activity of LY4101174 Monotherapy: Overall response rate (ORR)
Time Frame: Up to Approximately 48 Months or 4 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Up to Approximately 48 Months or 4 Years

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
To evaluate the preliminary antitumor activity of LY4101174: Overall response rate (ORR)
Time Frame: Up to Approximately 48 Months or 4 Years
ORR per investigator assessed Response Evaluation Criteria in Solid Tumors, version 1.1 (RECIST 1.1)
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4101174: Duration of response (DOR)
Time Frame: Up to Approximately 48 Months or 4 Years
DOR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4101174: Time to response (TTR)
Time Frame: Up to Approximately 48 Months or 4 Years
TTR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4101174: Progression free survival (PFS)
Time Frame: Up to Approximately 48 Months or 4 Years
PFS per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4101174: Disease control rate (DCR)
Time Frame: Up to Approximately 48 Months or 4 Years
DCR per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To evaluate the preliminary antitumor activity of LY4101174: Overall survival (OS)
Time Frame: Up to Approximately 48 Months or 4 Years
OS per investigator assessed RECIST 1.1
Up to Approximately 48 Months or 4 Years
To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin)
Time Frame: First 4 cycles (56 days)
PK: Cmin of LY4101174
First 4 cycles (56 days)
To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)
Time Frame: First 4 cycles (56 days)
PK: AUC of LY4101174
First 4 cycles (56 days)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Eli Lilly and Company

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Loxo Oncology, Inc.

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Call 1-877-CTLILLY (1-877-285-4559) or 1-317-615-4559 Mon - Fri 8 AM - 8 PM Eastern time (UTC/GMT - 5 hours, EST), Eli Lilly and Company

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
March 5, 2024

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
March 1, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 1, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 26, 2024

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 26, 2024

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
February 2, 2024

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
May 22, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
May 20, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 18836
  • LOXO-ENC-23001 (Other Identifier: Eli Lilly and Company)
  • J5A-OX-JZWA (Other Identifier: Eli Lilly and Company)
  • 2023-509867-26-00 (Other Identifier: EU Trial Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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