Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer
Purpose
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
Eligibility
- Eligible Ages
- Over 18 Years
- Eligible Sex
- All
- Accepts Healthy Volunteers
- No
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 Design
- Phase
- Phase 1
- Study Type
- Interventional
- Allocation
- N/A
- Intervention Model
- Sequential Assignment
- Intervention Model Description
- 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.
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab |
|
Recruiting Locations
Duarte, California 91010
Irvine, California 92618
Orlando, Florida 32806
Janice Porter M Clinical Research Screening & Eligibility Manager
321-841-7246
janice.porter@orlandohealth.com
Tucker, Georgia 30084
Zion, Illinois 60099
New Brunswick, New Jersey 22908
Lake Success, New York 11042
Charlottesville, Virginia 22908
More Details
- Status
- Recruiting
- Sponsor
- Generate Biomedicines
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.