Overview
The purpose of this study is to assess the antitumor efficacy and safety of perioperative enfortumab vedotin (EV) plus pembrolizumab and radical cystectomy (RC) + pelvic lymph node dissection (PLND) compared with the current standard of care (neoadjuvant chemotherapy \[gemcitabine plus cisplatin\] and RC + PLND) for participants with MIBC who are cisplatin-eligible. The primary hypothesis is perioperative EV and pembrolizumab and RC + PLND (Arm A) will achieve superior event free survival (EFS) compared with neoadjuvant gemcitabine + cisplatin and RC + PLND (Arm B).
Principal investigator
Eligibility criteria
Inclusion Criteria:
* Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
* Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
* Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate organ function.
Exclusion Criteria:
* Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
* Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
* Has ≥N2 disease or metastatic disease (M1) as identified by imaging
* Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
* Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
* Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
* Has a known psychiatric or substance abuse disorder
* Has had an allogenic tissue/solid organ transplant
* Has ongoing sensory or motor neuropathy Grade 2 or higher
* Has active keratitis (superficial punctate keratitis) or corneal ulcerations
* Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms
* Have a histologically confirmed diagnosis of urothelial carcinoma (UC) / muscle invasive bladder cancer (MIBC) (T2-T4aN0M0 or T1-T4aN1M0) with predominant (≥50%) urothelial histology.
* Have clinically non-metastatic bladder cancer (N≤1 M0) determined by imaging (computed tomography (CT) or magnetic resonance imaging (MRI) of the chest/abdomen/pelvis
* Be deemed eligible for Radical Cystectomy (RC) + Pelvic Lymph Node Dissection (PLND)
* Have Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
* Have adequate organ function.
Exclusion Criteria:
* Has a known additional malignancy that is progressing or has required active anti-cancer treatment ≤3 years of study randomization with certain exceptions
* Has received any prior systemic treatment for MIBC or non-invasive muscle bladder cancer (NMIBC - prior treatment for NMIBC with intravesical BCG/chemotherapy is permitted) or prior therapy with an anti- programmed cell death 1 (PD-1), anti-programmed cell death ligand 1/ ligand 2 (PD-L1/L2), or anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)
* Has ≥N2 disease or metastatic disease (M1) as identified by imaging
* Is cisplatin-ineligible, as defined by meeting any one of the cisplatin ineligibility criteria as per protocol
* Has received prior systemic anticancer therapy including investigational agents within 3 years of randomization or any radiotherapy to the bladder
* Has undergone partial cystectomy of the bladder to remove any NMIBC or MIBC
* Has received a live or live attenuated vaccine within 30 days before the first dose of study intervention
* Has a diagnosis of immunodeficiency or has a known history of human immunodeficiency virus (HIV) infection. Hepatitis B infection or known active Hepatitis C infection
* Has a known psychiatric or substance abuse disorder
* Has had an allogenic tissue/solid organ transplant
* Has ongoing sensory or motor neuropathy Grade 2 or higher
* Has active keratitis (superficial punctate keratitis) or corneal ulcerations
* Has a history of uncontrolled diabetes defined as hemoglobin A1c (HbA1c) ≥8% or HbA1c 7% to \<8% with associated diabetes symptoms
For Referring Providers
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