GB-4362 combined 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
This study will test adding GB-4362 to enfortumab vedotin and pembrolizumab to see if it lowers treatment-related side effects like nerve damage in adults with advanced or metastatic urothelial cancer.
Quick facts
| Phase | Phase 1 |
|---|---|
| Study type | Interventional |
| Enrollment | 37 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Generate Biomedicines Industry-sponsored |
| Drugs / interventions | enfortumab, pembrolizumab, chemotherapy, prednisone |
| Locations | 2 sites (Orlando, Florida and 1 other locations) |
| Trial ID | NCT07484022 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1, open-label, multicenter dose-finding trial that gives GB-4362 together with standard-dose enfortumab vedotin and pembrolizumab to adults with locally advanced or metastatic urothelial cancer. GB-4362 is a monoclonal antibody designed to bind and neutralize free MMAE, the cytotoxic payload released from enfortumab vedotin that is linked to toxicities such as peripheral neuropathy. The study uses a cohort-based dose escalation to identify safety, dose-limiting toxicities, and PK/PD effects, followed by a dose expansion at the selected dose. Exploratory endpoints include measurement of free MMAE reduction, peripheral neuropathy outcomes, dose modifications of enfortumab vedotin, and descriptive anti-tumor activity.
Who should consider this trial
Good fit: Adults (≥18) with locally advanced or metastatic urothelial cancer who are planned to start enfortumab vedotin plus pembrolizumab, have ECOG 0–1 (ECOG 2 allowed in expansion), weigh ≥50 kg, and can consent and comply with study visits are eligible.
Not a fit: Patients who previously received enfortumab vedotin or other MMAE-containing antibody–drug conjugates, or who cannot safely receive enfortumab vedotin or pembrolizumab, are unlikely to benefit from this study.
Why it matters
Potential benefit: If successful, adding GB-4362 could reduce peripheral neuropathy and other off-target toxicities, allowing safer delivery of enfortumab vedotin.
How similar studies have performed: Enfortumab vedotin combined with pembrolizumab has demonstrated anti-tumor activity in urothelial cancer, but using an antibody like GB-4362 to neutralize free MMAE is a novel approach with limited prior clinical data.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Orlando, Florida and 1 other locations
- Orlando Health — Orlando, Florida, United States (Recruiting)
- Start New York, LLC — Lake Success, New York, United States (Recruiting)
Study contacts
- Study coordinator: Study Contact
- Email: clinicaltrials@generatebiomedicines.com
- Phone: (888) 5471235
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.