Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer

May 14, 2026 updated by: Generate Biomedicines

A Phase 1, Open-Label Study to Evaluate the Safety, Pharmacokinetics, and Pharmacodynamics of GB-4362 Administered With Enfortumab Vedotin and Pembrolizumab in Participants With Advanced Urothelial Cancer

The purpose of this study is to evaluate the safety and tolerability of an investigational drug called GB-4362 when it is given together with enfortumab vedotin and pembrolizumab in adults with advanced or metastatic urothelial cancer. GB-4362 is a monoclonal antibody designed to bind and neutralize free monomethyl auristatin E (MMAE), a chemotherapy payload released from enfortumab vedotin that is associated with side effects such as peripheral neuropathy.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This is a Phase 1, open-label, multicenter, dose-finding study designed to evaluate the safety, pharmacokinetics (PK), and pharmacodynamics (PD) of GB-4362 administered in combination with standard-of-care enfortumab vedotin and pembrolizumab in participants with locally advanced or metastatic urothelial cancer.

Enfortumab vedotin is an antibody-drug conjugate containing the cytotoxic payload monomethyl auristatin E (MMAE). Systemic exposure to unconjugated (free) MMAE has been associated with dose-limiting toxicities, including peripheral neuropathy. GB-4362 is a monoclonal antibody designed to selectively bind and neutralize free MMAE in circulation, with the goal of reducing off-target toxicity while preserving the anti-tumor activity of enfortumab vedotin.

The study consists of two parts: dose escalation and dose expansion. Multiple dose levels of GB-4362 will be evaluated using a cohort-based escalation design to assess safety, identify dose-limiting toxicities, and characterize PK and PD, including the extent of free MMAE reduction. Dose escalation decisions will be reviewed by a Safety Monitoring Committee.

Following dose escalation, a dose expansion phase will enroll additional participants at the selected GB-4362 dose level to further evaluate safety, PK and PD. Exploratory assessments will include evaluation of peripheral neuropathy, dose modifications of enfortumab vedotin, and descriptive analyses of anti-tumor activity.

Study Type

Interventional

Enrollment (Estimated)

37

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
    • California
      • Duarte, California, United States, 91010
    • Florida
      • Orlando, Florida, United States, 32806
        • Recruiting
        • Orlando Health
        • Contact:
    • Georgia
      • Tucker, Georgia, United States, 30084
    • Illinois
      • Zion, Illinois, United States, 60099
    • New York

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

  • Planned to receive standard-of-care treatment with enfortumab vedotin (EV) (starting dose 1.25 mg/kg) in combination with pembrolizumab for locally advanced or metastatic urothelial cancer.
  • Age ≥18 years.
  • ECOG Performance Status score of 0 or 1 (ECOG 2 excluded in Dose Escalation but allowed in Dose Expansion).
  • Weight ≥50 kg at screening.
  • Life expectancy ≥3 months, as determined by the investigator.
  • Participants must provide written informed consent before any study-related activities are carried out and must be able to understand the nature and purpose of the study, including potential risks and adverse effects.
  • Willing and able to comply with all study assessments and adhere to the protocol schedule and restrictions.

Exclusion Criteria

  • Previously received enfortumab vedotin (EV) or other MMAE-based antibody-drug conjugates (ADCs).
  • Received anti-cancer treatment with chemotherapy, biologics, or investigational agents within 4 weeks before the first dose of EV/pembrolizumab.
  • Uncontrolled diabetes.
  • Active CNS metastases. Participants with treated CNS metastases are permitted if all of the following criteria are met:
  • CNS metastases have been clinically stable for at least 4 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.
  • The participant is on a stable dose of ≤10 mg/day of prednisone or equivalent for at least 2 weeks (if requiring steroid treatment).
  • The participant does not have leptomeningeal disease.
  • Ongoing clinically significant toxicity associated with prior treatment (including radiotherapy or surgery) that has not resolved to Grade ≤1 or returned to baseline.
  • History of a severe (Grade ≥3) allergic or infusion-related reaction to any monoclonal antibody.
  • Another underlying medical condition that, in the opinion of the investigator, would impair the ability of the participant to receive or tolerate the planned treatment and follow-up.
  • Known psychiatric or substance abuse disorders that would interfere with cooperating with study requirements

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: N/A
  • Interventional Model: Sequential Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab
Drug: GB-4362
GB-4362 is an investigational monoclonal antibody
Drug: enfortumab vedotin (EV)
Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 that delivers the cytotoxic payload monomethyl auristatin E (MMAE).
Drug: Pembrolizumab
Pembrolizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor administered as standard-of-care therapy for advanced urothelial cancer.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Incidence of AEs and SAEs
Time Frame: From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Pharmacokinetics of GB-4362
Time Frame: From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
Maximum plasma concentration (Cmax) of GB-4362 following administration with enfortumab vedotin and pembrolizumab.
From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
Reduction of Free MMAE Levels
Time Frame: From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
Immunogenicity of GB-4362
Time Frame: From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).
Incidence of treatment emergent anti-drug antibody against GB-4362
From first dose of GB-4362 through 18 weeks after the last dose of GB-4362 (or prior to initiation of subsequent anti-cancer therapy, whichever occurs first).

Collaborators and Investigators

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

Sponsor

Generate Biomedicines

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 (Estimated)

April 1, 2026

Primary Completion (Estimated)

June 1, 2027

Study Completion (Estimated)

December 1, 2027

Study Registration Dates

First Submitted

February 27, 2026

First Submitted That Met QC Criteria

March 16, 2026

First Posted (Actual)

March 19, 2026

Study Record Updates

Last Update Posted (Actual)

May 15, 2026

Last Update Submitted That Met QC Criteria

May 14, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • GB-4362-101

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.

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