Status:
ACTIVE_NOT_RECRUITING
A Study of Enfortumab Vedotin Alone or With Other Therapies for Treatment of Urothelial Cancer
Lead Sponsor:
Astellas Pharma Global Development, Inc.
Collaborating Sponsors:
Merck Sharp & Dohme LLC
Seagen Inc.
Conditions:
Carcinoma, Transitional Cell
Urinary Bladder Neoplasms
Eligibility:
All Genders
18+ years
Phase:
PHASE1
PHASE2
Brief Summary
This study will test an experimental drug (enfortumab vedotin) alone and with different combinations of anticancer therapies. Pembrolizumab is an immune checkpoint inhibitor (CPI) that is used to trea...
Detailed Description
This study will examine the safety and anticancer activity of enfortumab vedotin (EV) given intravenously as monotherapy and in combination with other anticancer therapies as first line (1L) and secon...
Eligibility Criteria
Inclusion
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K.
- Histologically documented la/mUC, including squamous differentiation or mixed cell types.
- An Eastern Cooperative Oncology Group (ECOG) Performance Status score of 0, 1 or 2: Participants with ECOG performance status of 2 must meet the following additional criteria: hemoglobin ≥10 g/dL, GFR ≥50 mL/min, may not have NYHA Class III heart failure.
- Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
- Dose-escalation cohorts: Ineligible for first-line cisplatin-based chemotherapy and no prior treatment for la/mUC, or have disease progression following at least 1 platinum-containing treatment.
- Cohort A: Ineligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence.
- Cohort D: Eligible for cisplatin-based chemotherapy and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort E: Ineligible for cisplatin-based chemotherapy, eligible for carboplatin, and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine.
- Cohort G: Eligible for platinum-based chemotherapy (either cisplatin or carboplatin) and no prior treatment for la/mUC. No prior adjuvant/neoadjuvant platinum-based therapy in at least 12 months.
- Cohort K: Ineligible for cisplatin-based chemotherapy due to at least 1 of the following: Glomerular filtration rate (GFR) \<60 mL/min and ≥30 mL/min, ECOG performance status of 2, NCI CTCAE Version 4.03 Grade ≥2 hearing loss, New York Heart Association (NYHA) Class III heart failure. No prior systemic treatment for locally advanced or metastatic disease. No adjuvant/neoadjuvant platinum-based therapy within 12 months prior to randomization.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.
- Histologically confirmed MIBC with predominant \>50% urothelial histology: Cohorts H and J: Clinical stage cT2-T4aN0M0; Cohort L: Clinical stage cT2-T4aN0M0 or cT1-T4aN1M0: Participants with pT1 disease are eligible only if they have N1 disease on imaging. Mixed cell types are eligible if urothelial cancer is predominant (\>50%); Participants with plasmacytoid and/or neuroendocrine tumors are ineligible regardless of component percentage. Urothelial tumors not originating in the bladder (eg, upper tract tumors, urethral tumors) are ineligible.
- Must be cisplatin-ineligible.
- Cohort-specific eligibility: Cohort J, H, and L: No prior systemic treatment, chemoradiation, or radiation therapy for MIBC. May have received prior intravesical Bacillus Calmette-Guerin (BCG) or intravesical chemotherapy for non-MIBC; Cohort J: Eligible for pembrolizumab.
- ECOG performance status of 0, 1, or 2.
- Anticipated life expectancy of ≥3 months.
- Tumor samples with an associated pathology report from the diagnostic transurethral resection of a bladder tumor done 90 days prior to the first dose of study treatment must be available prior to enrollment and determined to be sufficient for pathology review and biomarker analysis.
- Participants must be deemed eligible for RC+PLND.
Exclusion
- la/mUC - Cohorts A, B, D, E, F, G, and K
- Received any prior treatment with a PD-1 inhibitor, PD-L1 inhibitor, or PD-L2 inhibitor, except Cohort F.
- Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, OX-40 agonists, or cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitors (except Cohort F).
- Ongoing sensory or motor neuropathy Grade 2 or higher.
- Active central nervous system (CNS) metastases.
- Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
- Conditions requiring high doses of steroids or other immunosuppressive medications.
- Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- Uncontrolled diabetes mellitus.
- MIBC - Cohorts H, J, and L
- Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
- Received any prior treatment with a CPI.
- Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
- For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
- Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
- Ongoing sensory or motor neuropathy Grade 2 or higher.
- Conditions requiring high doses of steroids or other immunosuppressive medications.
- Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer.
- Participants with a history of another invasive malignancy within 3 years before first dose of study drug.
Key Trial Info
Start Date :
October 11 2017
Trial Type :
INTERVENTIONAL
Allocation :
ACTUAL
End Date :
September 11 2026
Estimated Enrollment :
348 Patients enrolled
Trial Details
Trial ID
NCT03288545
Start Date
October 11 2017
End Date
September 11 2026
Last Update
November 10 2025
Active Locations (106)
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1
Alaska Urological Institute
Anchorage, Alaska, United States, 99503
2
Banner MD Anderson Cancer Center
Gilbert, Arizona, United States, 85234
3
Mayo Clinic Arizona
Phoenix, Arizona, United States, 85054
4
Arizona Oncology Associates, PC - HOPE
Tucson, Arizona, United States, 85710