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

NCT07484022 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: GB-4362-101
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

Advanced Urothelial Cancer; Metastatic Urothelial Carcinoma

Keywords

GB-4362; Enfortumab Vedotin; Pembrolizumab; Peripheral Neuropathy; Antibody-Drug Conjugate; MMAE; Phase 1 Oncology; Dose Escalation; Dose Expansion

Outcome Measures

Primary Outcomes (1)

• Incidence of AEs and SAEs

  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 Outcomes (3)

• Pharmacokinetics of 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).

• Reduction of Free MMAE Levels

  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

  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).

Study Arms (1)

GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab

EXPERIMENTAL

Drug: GB-4362; Drug: enfortumab vedotin (EV); Drug: Pembrolizumab

Interventions

GB-4362 DRUG

GB-4362 is an investigational monoclonal antibody

GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab

enfortumab vedotin (EV) DRUG

Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 that delivers the cytotoxic payload monomethyl auristatin E (MMAE).

GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab

Pembrolizumab DRUG

Pembrolizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor administered as standard-of-care therapy for advanced urothelial cancer.

GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Generate Biomedicines: lead

Study Sites (7)

City of Hope

Duarte, California, 91010, United States

RECRUITING

Orlando Health

Orlando, Florida, 32806, United States

RECRUITING

Southeastern Regional Medical Center

Tucker, Georgia, 30084, United States

RECRUITING

Midwestern Regional Medical Center

Zion, Illinois, 60099, United States

RECRUITING

Start New York, LLC

Lake Success, New York, 11042, United States

RECRUITING

MSK

New York, New York, 10065, United States

RECRUITING

The University of Virgina

Charlottesville, Virginia, 22908, United States

RECRUITING

MeSH Terms

Conditions

Carcinoma, Transitional Cell; Peripheral Nervous System Diseases

Interventions

enfortumab vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neuromuscular Diseases; Nervous System Diseases

Central Study Contacts

Study Contact

CONTACT

(888) 5471235; clinicaltrials@generatebiomedicines.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is an open-label, sequential dose-escalation and dose-expansion study in which participants are enrolled in cohorts to receive increasing dose levels of GB-4362 administered in combination with standard-of-care enfortumab vedotin and pembrolizumab. Dose escalation decisions are based on cumulative safety and pharmacodynamic data from previously enrolled participants.

Study Record Dates

• First Submitted: February 27, 2026
• First Posted: March 19, 2026
• Study Start: June 1, 2026
• Primary Completion (Estimated): June 1, 2027
• Study Completion (Estimated): December 1, 2027
• Last Updated: June 3, 2026

Record last verified: 2026-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)