GB-4362 combined with enfortumab vedotin and pembrolizumab for advanced urothelial cancer

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

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.

Why it matters

Who can join: the full rules

Inclusion Criteria

* Planned to initiate, or (for dose escalation only) already receiving, 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).
* 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

* 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.
* No Grade \> 1 sensory or motor peripheral neuropathy.
* 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 it's running

• City of Hope
  Duarte, California, United States Recruiting
• COH Lennar
  Irvine, California, United States Recruiting
• Orlando Health
  Orlando, Florida, United States Recruiting
• COH Atlanta
  Tucker, Georgia, United States Recruiting
• COH Chicago
  Zion, Illinois, United States Recruiting
• Rutgers
  New Brunswick, New Jersey, United States Recruiting

Study contacts

• Study coordinator: Study Contact
• Email: clinicaltrials@generatebiomedicines.com
• Phone: (888) 5471235

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

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• Peripheral neuropathy during perioperative therapy with enfortumab vedotin and pembrolizumab in muscle-invasive urothelial cancer

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• Enfortumab Vedotin, Pembrolizumab, and Quemliclustat for unresectable or metastatic urothelial cancer

  This trial tests a three-drug combination to see if it can safely treat unresectable or metastatic urothelial cancer in adults.

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How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.