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

April 18, 2024 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 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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1a/1b multicenter, open-label study in participants with advanced or metastatic solid tumor malignancies known to express Nectin 4. 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.

Study Type

Interventional

Enrollment (Estimated)

280

Phase

  • 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 Locations

  • United States
    • Massachusetts
      • Boston, Massachusetts, United States, 02114
        • Recruiting
        • Massachusetts General Hospital
    • Missouri
      • Saint Louis, Missouri, United States, 63110
        • Not yet recruiting
        • Washington University School of Medicine
    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
      • New York, New York, United States, 10065
        • Not yet recruiting
        • Memorial Sloan Kettering Cancer Center
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599-7305
        • Not yet recruiting
        • University of North Carolina Medical Center
    • Texas
      • Dallas, Texas, United States, 75390-8884
        • Not yet recruiting
        • UT Southwestern Medical Center
      • San Antonio, Texas, United States, 78229-3307
        • Recruiting
        • 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

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 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

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
Intervention / Treatment
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

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

Outcome Measure
Measure Description
Time Frame
To characterize the pharmacokinetics (PK) properties of LY4101174: Minimum Plasma Concentration (Cmin)
Time Frame: Cycle 1 (14 Days)
PK: Cmin of LY4101174
Cycle 1 (14 Days)
To characterize the PK properties of LY4101174: Area under the concentration versus time curve (AUC)
Time Frame: Cycle 1 (14 Days)
PK: AUC of LY4101174
Cycle 1 (14 Days)
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

Collaborators and Investigators

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

Sponsor

Eli Lilly and Company

Collaborators

Loxo Oncology, Inc.

Investigators

  • Study Director: Xiaojian (Thomas) Xu, Loxo Oncology, Inc.

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)

March 5, 2024

Primary Completion (Estimated)

August 26, 2026

Study Completion (Estimated)

March 4, 2027

Study Registration Dates

First Submitted

January 26, 2024

First Submitted That Met QC Criteria

January 26, 2024

First Posted (Actual)

February 2, 2024

Study Record Updates

Last Update Posted (Actual)

April 19, 2024

Last Update Submitted That Met QC Criteria

April 18, 2024

Last Verified

April 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • LOXO-ENC-23001
  • 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

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.

Clinical Trials on Cervical Cancer

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Vietnam

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

3
Subscribe