A Phase 3, Randomized, Open-label Study to Evaluate Perioperative Enfortumab Vedotin Plus Pembrolizumab (MK-3475) Versus Neoadjuvant Gemcitabine and Cisplatin in Cisplatin-eligible Participants with Muscle-invasive Bladder Cancer (KEYNOTE-B15 / EV-304)
Perioperative EV + Pembrolizumab vs Neoadjuvant Chemotherapy for Cisplatin-eligible MIBC
- 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
- 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 percent or HbA1c 7 percent to <8 percent with associated diabetes symptoms
18age old over
No limit
Both
Muscle Invasive Bladder Cancer
Arm A
Biological: Pembrolizumab
200 mg of Pembrolizumab IV infusion, on Day 1 Q3W for 4 cycles (each cycle length equal 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 Q3W for 13 cycles in postoperative phase (up to approximately 9 months). The total duration of treatment is up to approximately 1 year.
Biological: Enfortumab vedotin (EV)
1.25 mg/kg of EV IV infusion, on Day 1 and Day 8 Q3W for 4 cycles (each cycle length equal 21 days) in preoperative phase (up to approximately 3 months) and on Day 1 and Day 8 Q3W for 5 cycles (each cycle length equal 21 days) in postoperative phase (up to approximately 4 months). The total duration of treatment is up to approximately 7 months.
Procedure: RC plus PLND
Curative intent RC plus PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC plus PLND to be done approximately at 15 weeks from randomization).
Arm B
Drug: Gemcitabine
1000 mg/m2 of Gemcitabine IV infusion, Day 1 and Day 8 Q3W for 4 cycles in preoperative phase (up to approximately 3 months)
Drug: Cisplatin
70 mg/m2 of Cisplatin IV infusion, Day 1, Q3W for 4 cycles in preoperative phase (up to approximately 3 months)
Procedure: RC plus PLND
Curative intent RC plus PLND surgery will be administered to all participants randomized to Arm A and B after completion of preoperative systemic treatment (RC plus PLND to be done approximately at 15 weeks from randomization).
- Overall Survival (OS)
- Disease-Free Survival (DFS)
- Pathological Downstaging Rate (pDSR)
- Participants experiencing adverse events (AEs)
- Participants discontinuing study drug due to AEs
- Participant experiencing perioperative complications
- European Organization for Research and Treatment of Cancer QoL questionnaire-Core 30 (EORTC QLQ-C30)
- Bladder Cancer Index (BCI)
- Quality of Life-5 Dimensions, 5-level Questionnaire (EQ-5D-5L)
MSD K.K.
Institutional Review Board of Gifu University Hospital
