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A study of enfortumab vedotin alone or in combination with other anticancer therapies for the treatment of urothelial cancer
EU CTIS ID: 2023-503391-24-00
What this study is testing
Locally Advanced or Metastatic Urothelial Cancer : ● To assess the safety and tolerability of enfortumab vedotin in combination with pembrolizumab and/or chemotherapy. Randomized Cohort K: ● To assess the antitumor activity of enfortumab vedotin monotherapy or enfortumab vedotin in combination with pembrolizumab as measured by ORR per RECIST Version 1.1 by blinded independent central review (BICR). Muscle Invasive Bladder Cancer: ● To assess the antitumor activity of neoadjuvant and perioperative enfortumab vedotin monotherapy or neoadjuvant enfortumab vedotin in combination with pembrolizumab as measured by the pathological complete response (pCR) rate, defined as the absence of viable tumor (pT0N0) in examined tissue from radical cystectomy (RC) and pelvic lymph node dissection (PLND) by central pathology review
- Therapeutic exploratory (Phase II)
A plain-language read of the study's public EU CTIS listing. The study team confirms the details.
Who can take part
You may be able to join if
- 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.
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Must be cisplatin-ineligible
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: 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.
You likely can't join if
- 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.
- MIBC - Cohorts H, J, and L: Received any prior treatment with a CPI
- MIBC - Cohorts H, J, and L: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
- MIBC - Cohorts H, J, and L: For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
- MIBC - Cohorts H, J, and L: Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
- MIBC - Cohorts H, J, and L: Ongoing sensory or motor neuropathy Grade 2 or higher.
See the full eligibility criteria
Who can join
- 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.
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Must be cisplatin-ineligible
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: 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.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: ECOG performance status of 0, 1, or 2.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Anticipated life expectancy of ≥3 months.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: 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.
- Muscle Invasive Bladder Cancer (MIBC)- Cohorts H, J and L.: Participants must be deemed eligible for RC+PLND.
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K:Eligible for pembrolizumab (Dose-escalation cohorts, Cohorts A, B, G and K Combination Arm).
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort B: Must have disease progression during/following treatment with at least 1 platinum-containing regimen for la/mUC or disease recurrence
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: 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
- Locally advanced or metastatic urothelial cancer (la/mUC) - Cohorts A, B, D, E, F, G and K: Cohort F: Ineligible for platinum-based chemotherapy, or disease progression during/following at least 1 prior treatment for la/mUC. Eligible for gemcitabine
What rules you out
- 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.
- MIBC - Cohorts H, J, and L: Received any prior treatment with a CPI
- MIBC - Cohorts H, J, and L: Received any prior treatment with stimulatory or co-inhibitory T-cell receptor agents, such as CD137 agonists, CTLA-4 inhibitors, or OX-40 agonists.
- MIBC - Cohorts H, J, and L: For participants in Cohort H, evidence of nodal disease on imaging. For participants in Cohort L, ≥N2 nodal disease on imaging.
- MIBC - Cohorts H, J, and L: Participant has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC.
- MIBC - Cohorts H, J, and L: Ongoing sensory or motor neuropathy Grade 2 or higher.
- MIBC - Cohorts H, J, and L: Conditions requiring high doses of steroids or other immunosuppressive medications.
- MIBC - Cohorts H, J, and L: Prior treatment with enfortumab vedotin or other MMAE-based ADCs for urothelial cancer
- MIBC - Cohorts H, J, and L: Participants with a history of another invasive malignancy within 3 years before first dose of study drug.
- la/mUC - Cohorts A, B, D, E, F, G, and K: 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).
- la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing sensory or motor neuropathy Grade 2 or higher.
- la/mUC - Cohorts A, B, D, E, F, G, and K: Active central nervous system (CNS) metastases.
- la/mUC - Cohorts A, B, D, E, F, G, and K: Ongoing clinically significant toxicity (Grade 2 or greater) associated with prior treatment (including radiotherapy or surgery).
- la/mUC - Cohorts A, B, D, E, F, G, and K: Conditions requiring high doses of steroids or other immunosuppressive medications.
- la/mUC - Cohorts A, B, D, E, F, G, and K: Prior treatment with enfortumab vedotin or other monomethyl auristatin E (MMAE)-based antibody-drug conjugates (ADCs).
- la/mUC - Cohorts A, B, D, E, F, G, and K: Uncontrolled diabetes mellitus.
- MIBC - Cohorts H, J, and L: Received prior systemic treatment, chemoradiation, and/or radiation therapy of muscle invasive bladder cancer.
The study team makes the final eligibility decision.
Where it's taking place
- Canada
- United States
Questions & answers
Do participants get paid in this trial?
This listing doesn't specify compensation. Many trials still reimburse travel or offer a stipend, so it's worth asking the study team when you connect.
Is it free to join, and do I need insurance?
Searching and applying through BridgeMD is free. In clinical trials the study-related treatment and visits are generally provided at no cost to you. You usually don't need insurance to take part - confirm specifics with the study team.
How long does this study last?
The listing doesn't state an exact length. The study team walks you through the schedule and number of visits before you decide to enroll.
Who can join this trial?
This study is enrolling all sexes, 65+ years, 18-64 years. The study team makes the final eligibility decision.
Where is this trial taking place?
Study sites include Canada; United States. Enter your location above to see the nearest site and check your eligibility.
Explore other conditions
BridgeMD is an information and trial-matching tool - not medical advice, and not the study sponsor. Details come from EU CTIS; the study team decides eligibility.