5580 Background: Mirvetuximab soravtansine (MIRV), an antibody-drug conjugate targeting folate receptor alpha (FRα), demonstrated an improvement in progression-free survival (PFS), overall response rate (ORR), and overall survival (OS) in patients (pts) with high-grade serous PROC compared to ICC (Moore K et al. N Engl J Med 2023;389:2162-74). Here, we present safety and efficacy data in an older population (≥ 65) from the intent-to-treat population. Methods: 453 PROC pts with high FRα expression (VENTANA FOLR1 [FOLR1-2.1] RxDx Assay) with 1-3 prior therapies were randomized 1:1 to MIRV 6 mg/kg, adjusted ideal body weight, Day 1 of a 21-day cycle or ICC: paclitaxel, pegylated liposomal doxorubicin, or topotecan. The primary efficacy endpoint was PFS by investigator (INV) with key secondary endpoints ORR, OS, and patient-reported outcomes in hierarchical order; other endpoints included safety, tolerability, and duration of response. Results: With a data cutoff of March 6, 2023, 107 pts ≥ 65 were randomized to the MIRV arm; 92 pts ≥ 65 were randomized to the ICC arm. Baseline characteristics were well balanced across arms; the median age was 71 years for MIRV and 70 for ICC arm. In the MIRV arm, 57% had prior bevacizumab vs. 67% in the ICC arm, and 57% had prior PARPi experience vs. 58% in the ICC arm in pts ≥ 65. In the MIRV arm, 15% had one, 36% had two, and 49% had three prior lines of therapy, respectively, and in the ICC arm, 18% had one, 39% had two, and 42% had three prior lines of therapy, respectively. The nominal PFS HR was 0.62 (0.45, 0.86), favoring MIRV; nominal OS HR was 0.57 (0.37, 0.87), favoring MIRV, and the overall response rate was 39.3% for MIRV vs. 17.4% for ICC in pts ≥ 65. Compared with ICC, pts on MIRV were associated with lower rates of grade 3+ treatment-emergent AEs (45% vs 58%) and serious AEs (24% vs 38%). TEAEs leading to dose reductions in MIRV pts ≥ 65 compared to ICC were 34% vs 30%, dose delays were 49% vs 57%, and discontinuations were 10% vs. 23%, respectively. Ocular, gastrointestinal, and neurosensory adverse events were comparable to the intent to treat population. Additional safety data will be presented. Conclusions: MIRV is the first treatment to demonstrate a PFS, ORR, and OS benefit in PROC compared to ICC. MIRV demonstrated a longer PFS, OS, and higher ORR vs ICC in the older population. Importantly, MIRV had fewer dose discontinuations than ICC, suggesting that TEAEs were more manageable The efficacy data and the well-characterized safety profile support MIRV as the standard of care for pts with FRα positive PROC across all ages. Clinical trial information: NCT04209855 .