Advanced Urothelial CancerPhase 1NCT07484022
Study of GB-4362 With Enfortumab Vedotin and Pembrolizumab for Advanced Urothelial Cancer
A Phase 1 study testing GB-4362, enfortumab vedotin (EV) and Pembrolizumab in people with Advanced Urothelial Cancer and Metastatic Urothelial Carcinoma, run by Generate Biomedicines at 10 sites in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Advanced Urothelial Cancer, Metastatic Urothelial Carcinoma
- What is being tested?
- GB-4362, enfortumab vedotin (EV) and Pembrolizumab
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 37 participants
- Where
- 10 sitesUnited States
- Study dates
- 8 Jun 2026to Dec 2027
- Phase
- Phase 1
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
10 sites in 1 country. Contact the study team or a site near you to ask about taking part.
10 sites in 1 country
United States10 sites, 10 recruiting
- Recruiting
The University of Virgina
Charlottesville, Virginia, 22908
Clinical Trials Navigator, 434-982-0539, uvacancertrials@uva.com
- Recruiting
City of Hope
Duarte, California, 91010
Susan Hmwe Manager Clinical Research, 626-218-4081, shmwe@coh.org
- Recruiting
MDACC
Houston, Texas, 77030
Cindy Jiang PI, 713-876-4652, CYJiang@mdanderson.org
- Recruiting
COH Lennar
Irvine, California, 92618
Susan Hmwe Manager Clinical Research, 626-218-4081, shmwe@coh.org
- Recruiting
Start New York, LLC
Lake Success, New York, 11042
Camilita Goberdhan, 347-476-1959, camilita.goberdhan@startresearch.com
- Recruiting
Rutgers
New Brunswick, New Jersey, 08903
Kassie DiOrio Manager, 732-454-9795, kassie.diorio@rutgers.edu
- Recruiting
MSK
New York, New York, 10065
Sam Funt PI, 646-888-4770, funts@mskcc.org
- Recruiting
Orlando Health
Orlando, Florida, 32806
Janice Porter M Clinical Research Screening & Eligibility Manager, 321-841-7246, janice.porter@orlandohealth.com
- Recruiting
COH Atlanta
Tucker, Georgia, 30084
Susan Hmwe Manager Clinical Research, 626-218-4081, shmwe@coh.org
- Recruiting
COH Chicago
Zion, Illinois, 60099
Susan Hmwe Manager Clinical Research, 626-218-4081, shmwe@coh.org
About this study
Official title: 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
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.
Read the 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.
- Being tested
- GB-4362, enfortumab vedotin (EV), Pembrolizumab
- Keywords
- GB-4362, Enfortumab Vedotin, Pembrolizumab, Peripheral Neuropathy, Antibody-Drug Conjugate, MMAE, Phase 1 Oncology, Dose Escalation, Dose Expansion
- Medical subject headings
- Carcinoma, Transitional Cell, Peripheral Nervous System Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GB-4362Drug
GB-4362 is an investigational monoclonal antibody
enfortumab vedotin (EV)Drug
Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 that delivers the cytotoxic payload monomethyl auristatin E (MMAE).
PembrolizumabDrug
Pembrolizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor administered as standard-of-care therapy for advanced urothelial cancer.
| Study group | Role | What they receive |
|---|---|---|
| GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab | Experimental | Not described Receives: Drug: GB-4362; Drug: enfortumab vedotin (EV); Drug: Pembrolizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of AEs and SAEs
Measured: 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
Maximum plasma concentration (Cmax) of GB-4362 following administration with enfortumab vedotin and pembrolizumab.
Measured: 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
Measured: 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
Incidence of treatment emergent anti-drug antibody against GB-4362
Measured: 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).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Mar 2026
- Study start8 Jun 2026
- Primary completionJun 2027 (estimated)
- Study completionDec 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Advanced Urothelial CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- 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.
- Masking
- None (open label)
- Enrolment
- 37 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Generate Biomedicines
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07484022
- Sponsor's protocol ID
- GB-4362-101
- Status last verified
- Oct 2026
- First submitted
- 27 Feb 2026
- Last updated
- 13 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 13 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT07484022
- Acronym / sponsor ID
- GB-4362-101
- Keywords
- GB-4362, Enfortumab Vedotin, Pembrolizumab, Peripheral Neuropathy, Antibody-Drug Conjugate, MMAE, Phase 1 Oncology, Dose Escalation
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 37 participants (estimated)
- Lead sponsor
- Generate BiomedicinesIndustry (pharma, biotech, devices)
- Study start
- 8 Jun 2026 (actual)
- Primary completion
- Jun 2027 (estimated)
- Study completion
- Dec 2027 (estimated)
- First posted
- 19 Mar 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 1
- 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.
| Arm | Type | Receives |
|---|---|---|
| GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab | Experimental | Drug: GB-4362, Drug: enfortumab vedotin (EV), Drug: Pembrolizumab |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| GB-4362GB-4362 is an investigational monoclonal antibody | Drug | GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab |
| enfortumab vedotin (EV)Enfortumab vedotin is an antibody-drug conjugate targeting Nectin-4 that delivers the cytotoxic payload monomethyl auristatin E (MMAE). | Drug | GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab |
| PembrolizumabPembrolizumab is a programmed death-1 (PD-1) immune checkpoint inhibitor administered as standard-of-care therapy for advanced urothelial cancer. | Drug | GB-4362 in Combination With Enfortumab Vedotin and Pembrolizumab |
Primary outcome
Incidence of AEs and SAEs
Time frame: 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).
3 secondary outcomes
Pharmacokinetics of GB-4362
Time frame: 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
Time frame: 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
Time frame: 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).
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Oct 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
10 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing GB-4362, enfortumab vedotin (EV) and Pembrolizumab in people with Advanced Urothelial Cancer and Metastatic Urothelial Carcinoma, run by Generate Biomedicines at 10 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 13 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 10 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Study Contact ((888) 5471235, clinicaltrials@generatebiomedicines.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence of AEs and SAEs (time frame: 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).). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Oct 2026.