Enfortumab Vedotin Schedule De-escalation in Metastatic Urothelial Carcinoma

NCT05923190 | Active Not Recruiting Phase 2 DMC FDA Drug

• 2 other identifiers: 23-1008GU-217
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

Brief Summary

This is a non-randomized two arm open-label phase 2 pilot study in adult subjects with locally advanced or metastatic urothelial cancer. The study will investigate an alternative administration schedule of EV given as monotherapy and in combination with pembrolizumab.

Conditions

Urothelial Carcinoma; Metastatic Urothelial Carcinoma; Locally Advanced Urothelial Carcinoma

Outcome Measures

Primary Outcomes (1)

• Duration of clinical benefit

  Duration of Clinical Benefit (DoCB) in patients undergoing EV schedule de-escalation in the EV monotherapy cohort. DoCB is defined as time from initiating treatment to disease progression or death in patients who achieve complete response, partial response, or stable disease (per RECIST v1.1)

  8 months

Secondary Outcomes (2)

• Overall survival

  5 years

• Time to next treatment

  5 years

Study Arms (2)

Enfortumab vedotin (EV) monotherapy

ACTIVE COMPARATOR

EV will be administered at standard dose of 1.25 mg/kg IV on days 1, 8 and 15 of a 28-day cycle for 3 cycles. First schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their first scan in the EV at 12 weeks. In these patients, EV will be administered on days 1 and 15 of a 28-day cycle. Second schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their second scan in the EV monotherapy (at 24 weeks). EV will be administered on day 1 of a 21-day cycle.

Drug: Enfortumab vedotin

EV/pembrolizumab

EXPERIMENTAL

EV will be administered at standard dose of 1.25 mg/kg IV on days 1 and 8 with pembrolizumab 200 mg IV on day 1 of a 21-day cycle for 6 cycles. Radiographic assessment will be conducted every 9 weeks. Schedule de-escalation of EV will occur in patients with disease control per RECIST v1.1 (complete response/partial response/stable disease) on their first scan in the EV/pembrolizumab arm at 9 weeks. In these patients EV and pembrolizumab will be administered on day 1 of a 21-day cycle.

Drug: Enfortumab vedotin; Drug: Pembrolizumab

Interventions

Pembrolizumab DRUG

Pembrolizumab will be administered on day 1 of a 21-day cycle

EV/pembrolizumab

Enfortumab vedotin DRUG

EV will be administered at standard dose of 1.25 mg/kg IV on days 1 and 8 with pembrolizumab 200 mg IV on day 1 of a 21-day cycle for 6 cycles

EV/pembrolizumab; Enfortumab vedotin (EV) monotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• EV monotherapy main cohort:
• Patients must have histologically and radiographically confirmed locally advanced or metastatic urothelial carcinoma.
• Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension in accordance with RECIST criteria v1.1
• Planned to receive EV as standard treatment for advanced urothelial cancer
• ECOG performance status 0-2
• Prior systemic therapy must have completed at least 14 days prior to initiating therapy.
• Age \> 18 years.
• Ability to understand and willingness to sign a written informed consent and HIPAA consent document
• Archival tumor biospecimen (when available) must be procured for correlative evaluation. If tumor tissue is not available or accessible despite good faith efforts, patient may still be treated on study. Formalin-fixed paraffin-embedded \[FFPE\] tissue block(s) or at least 15 unbaked, unstained slides are required. Tissue samples taken from a metastatic lesion prior to the start of screening are acceptable.
• Normal organ and marrow function as defined below.
• Absolute neutrophil count \> 1,000/mm3 unless patient has constitutional neutropenia
• Platelets \> 100,000/ul
• Hemoglobin \> 8.0 g/dL
• Alanine transaminase (ALT) and aspartate transaminase (AST) \<2.5X upper limit of normal (ULN) or \<3.5X ULN if liver metastases
• Creatinine Clearance \>20 ml/min

You may not qualify if:

• Both EV monotherapy and EV/pembrolizumab arms:
• Patients who have received prior monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs) for urothelial cancer.
• Grade 2 or higher baseline sensory or motor neuropathy.
• Uncontrolled diabetes (HbA1c \>8%)
• Patients with uncontrolled and untreated central nervous system (CNS) metastases.
• Prior radiation to CNS metastases is permitted.
• Prior history of CNS disease that has responded to previous systemic therapy is permitted only if no recurrence.
• Patient should not have leptomeningeal disease
• CNS metastases have been clinically stable for at least 6 weeks prior to screening and baseline scans show no evidence of new or enlarged metastasis.
• If requiring steroid treatment for CNS metastases, the patient is on stable dose \< 20 mg/day of prednisone or equivalent for at least 2 weeks prior to starting treatment
• Uncontrolled intercurrent illness including, but not limited to ongoing or active untreated infection, symptomatic congestive heart failure, unstable angina pectoris, symptomatic uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Subjects with a history of another invasive malignancy within 3 years before the first dose of study drug that cannot be watched and requires treatment, or any evidence of residual disease from a previously diagnosed malignancy that cannot be watched and requires treatment. Adjuvant hormonal therapy for breast cancer is allowed.
• Currently receiving systemic antimicrobial treatment for active infection (viral, bacterial, or fungal) at the time of first dose of enfortumab vedotin. Routine antimicrobial prophylaxis is permitted.
• Known HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with enfortumab vedotin.
• History of idiopathic pulmonary fibrosis; organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead

Study Sites (1)

Fox Chase Cancer Center - Philadelphia

Philadelphia, Pennsylvania, 19111-2497, United States

Location

MeSH Terms

Conditions

Carcinoma, Transitional Cell

Interventions

enfortumab vedotin; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms

Study Officials

• Pooja Ghatalia, MD

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 20, 2023
• First Posted: June 28, 2023
• Study Start: June 14, 2023
• Primary Completion (Estimated): July 1, 2028
• Study Completion (Estimated): July 1, 2029
• Last Updated: March 19, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)