Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer
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
Generate Biomedicines
37 participants
Apr 1, 2026
INTERVENTIONAL
Conditions
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.
Eligibility
Inclusion Criteria7
- 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 Criteria11
- 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
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Interventions
GB-4362 is an investigational monoclonal antibody
Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 that delivers the cytotoxic payload monomethyl auristatin E (MMAE).
Pembrolizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor administered as standard-of-care therapy for advanced urothelial cancer.
Locations(2)
View Full Details on ClinicalTrials.gov
For the most up-to-date information, visit the official listing.
NCT07484022