Core Insights - The approval of the combination therapy of Bemarituzumab and Pembrolizumab marks the first and currently only perioperative treatment option for muscle-invasive bladder cancer (MIBC) patients who are not suitable for cisplatin-based chemotherapy, significantly improving survival outcomes compared to standard surgery [1][2] Group 1: Treatment Approval and Efficacy - The FDA has approved the combination of Bemarituzumab (an antibody-drug conjugate targeting Nectin-4) and Pembrolizumab (a PD-1 inhibitor) for neoadjuvant treatment in adult patients with muscle-invasive bladder cancer [1] - The approval is based on the pivotal Phase III EV-303 study, which demonstrated a 60% reduction in the risk of recurrence, progression, or death compared to surgery alone, and a 50% reduction in mortality risk [1][2] - The combination therapy is expected to redefine treatment standards for cisplatin-ineligible MIBC patients, addressing a long-standing unmet medical need [2][3] Group 2: Clinical Study Results - In the EV-303 study, the event-free survival (EFS) rate for the combination therapy group was 74.7%, compared to 39.4% for the surgery-only group, with a median EFS not yet reached for the combination group versus 15.7 months for the surgery group [2] - The overall survival (OS) data indicated a two-year survival probability of 79.7% for the combination group, compared to 63.1% for the surgery group, with a median OS not yet reached for the combination group versus 41.7 months for the surgery group [2] Group 3: Safety Profile - The safety profile of the combination therapy aligns with previous reports, with no new safety signals identified [3] - Common adverse reactions (≥20%) included laboratory abnormalities such as elevated blood glucose and hemoglobin levels, as well as fatigue and rash [3] - The incidence of grade 3 or higher adverse events was 71.3% in the combination therapy group compared to 45.9% in the surgery group [3] Group 4: Ongoing Research - The ongoing Phase III EV-304 study is evaluating the combination of Bemarituzumab and Pembrolizumab in the perioperative setting for cisplatin-eligible MIBC patients [4]