Health TrialsbyHealthPanel

Enfortumab Vedotin Plus Pembrolizumab With Selective Bladder Sparing for Treatment of Muscle-invasive Bladder Cancer

ConditionMuscle Invasive Bladder Urothelial Carcinoma
Trial statusRecruiting
Trial phasePhase 2
Trial typeInterventional
Biological sexAll
Age18+
SponsorMatthew Galsky

About this trial

Patients with MIBC will receive 3 cycles (C1-C3) of induction enfortumab vedotin plus pembrolizumab followed by restaging including MRI of the bladder, urine cytology, and cystoscopy with TURBT of any visible tumor and/or resection site plus random biopsies using a recommended template. Patients achieving a stringently defined cCR (clinical complete response) will receive 14 cycles of "maintenance" treatment. Enfortumab vedotin will be administered during the first 6 cycles (C4-C9) of "maintenance" treatment and pembrolizumab will be given all 14 cycles (C4-C14). Patients with any residual disease at clinical restaging (i.e., \>cTa disease) will undergo cystectomy.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.

Age ≥ 18 years at the time of consent.

ECOG Performance Status of 0-1 within 28 days prior to registration.

Histological evidence of clinically localized muscle-invasive urothelial cancer of the bladder clinical stage T2-3N0M0. Participants with mixed histology are eligible provided the urothelial component is ≥50% with the following exceptions: (a) tumors with any degree of squamous differentiation are eligible provided there is a urothelial cancer component, (b) tumors that contain any component of neuroendocrine histology are not eligible. N0 will be considered as the absence of radiographically enlarged lymph nodes on baseline imaging (i.e., Patients with lymph nodes ≥1.5 cm in short axis on imaging are not eligible).

Disqualifiers

Pre-existing sensory or motor neuropathy Grade ≥ 2

Ongoing clinically significant toxicity (Grade 2 or higher with the exception of alopecia) associated with prior treatment (including systemic therapy, radiotherapy or surgery).

Prior systemic chemotherapy for muscle-invasive urothelial cancer of the bladder.

Prior malignancy active within the previous 2 years except for locally curable cancers that have been apparently cured. Patients with intermediate or lower risk prostate cancer as defined by the National Comprehensive Cancer Network (NCCN) risk stratification guidelines may be eligible for enrollment.

Trial design

Design model

Single group

Treatments tested in this trial

  • Enfortumab vedotin

    Drug

    1.25 mg/kg (maximum dose 125 mg)

  • Pembrolizumab

    Drug

    200 mg

Treatment groups

75 Participants
are divided into 1 treatment group
Group A: Enfortumab vedotin plus pembrolizumabExperimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

Complete response rate with enfortumab vedotin plus pembrolizumab for MIBC

Clinical complete response rate will be defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab

Time frame
9 weeks
2

Bladder-intact event-free survival (BIEFS) in patients achieving a clinical complete response

Estimate the 2-year bladder-intact event-free survival (BIEFS) in patients achieving a clinical complete response

Time frame
2 years

Secondary outcomes

1

Safety of enfortumab vedotin plus pembrolizumab

Safety will be determined according to the NCI Common Terminology Criteria for Adverse Events (NCI CTCAE) v5

Time frame
2 years
2

Positive predictive value (PPV) of cCR Patients

Estimate the positive predictive value (PPV) of cCR for 2-year metastasis-free survival

Time frame
2 years
3

Local recurrence-free survival

Estimate invasive local recurrence-free survival in patients achieving a clinical complete response and forgoing immediate cystectomy. Local recurrence free survival is defined as the time from initiation of treatment until the development of invasive local recurrences in the intact bladder.

Time frame
4 years
4

Association between clinical complete response (cCR) and bladder-intact event-free survival

Estimate association between clinical complete response defined as cT0 or cTa (low grade) disease at the time of restaging after 3 cycles of induction enfortumab vedotin plus pembrolizumab and bladder-intact event-free survival defined from initiation of treatment until radical cystectomy, evidence of unresectable or metastatic disease, or death due to any cause based on the Kaplan-Meier method .

Time frame
4 years

Other outcomes

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Matthew Galsky

Lead sponsor

Hoosier Cancer Research Network

Sponsor institution

Seagen Inc.

Collaborator

Astellas Pharma Inc

Collaborator

Merck Sharp & Dohme LLC

Collaborator

Icahn School of Medicine at Mount Sinai

Collaborator

Source ClinicalTrials.gov
Apply now