Background
MIRASOL (GOG 3045/ENGOT-ov55) was a phase III randomized open-label trial evaluating mirvetuximab soravtansine (MIRV) — a folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) conjugated to DM4 — versus investigator's choice chemotherapy (paclitaxel, PLD, or topotecan) in platinum-resistant ovarian, primary peritoneal, or fallopian tube cancer with high FRα expression. It was the first ADC to demonstrate a PFS and OS benefit in platinum-resistant ovarian cancer.
Interventions and follow up
Arm A: Investigator's choice chemotherapy (paclitaxel, pegylated liposomal doxorubicin, or topotecan)
Arm B: Mirvetuximab soravtansine (MIRV) 6 mg/kg (adjusted ideal body weight) IV q21d until progression
Primary endpoint: Investigator-assessed PFS (RECIST v1.1)
Key secondary: OS
mFollow-up: 13.1 months
Arm B: Mirvetuximab soravtansine (MIRV) 6 mg/kg (adjusted ideal body weight) IV q21d until progression
Primary endpoint: Investigator-assessed PFS (RECIST v1.1)
Key secondary: OS
mFollow-up: 13.1 months
Results
mPFS: 5.62 vs 3.98 months (HR 0.65, 95% CI 0.52–0.81, P<.001)
mOS: 16.46 vs 12.75 months (HR 0.67, 95% CI 0.50–0.89, P=.004)
ORR: 42.3% vs 15.9% (OR 3.81, P<.001)
DoR: median not reached (MIRV) vs 6.3 months (chemo)
mOS: 16.46 vs 12.75 months (HR 0.67, 95% CI 0.50–0.89, P=.004)
ORR: 42.3% vs 15.9% (OR 3.81, P<.001)
DoR: median not reached (MIRV) vs 6.3 months (chemo)
Adverse events
Overall: Grade ≥3 AEs 42% (MIRV) vs 54% (chemo); treatment discontinuation 16% vs 18%; fatigue 10% vs 11%
Ocular: blurred vision any grade 41% MIRV vs 2% chemo (Grade ≥3 8% vs <1%); keratopathy managed with cold packs and lubricating drops
Neurologic: peripheral neuropathy Grade ≥3 1% vs 7%
Ocular: blurred vision any grade 41% MIRV vs 2% chemo (Grade ≥3 8% vs <1%); keratopathy managed with cold packs and lubricating drops
Neurologic: peripheral neuropathy Grade ≥3 1% vs 7%
Conclusions
Mirvetuximab soravtansine significantly improved PFS, OS, and ORR versus chemotherapy in FRα-high platinum-resistant ovarian cancer, with a more favorable toxicity profile (lower Grade ≥3 AEs) than chemotherapy, establishing MIRV as a new standard of care for FRα-positive platinum-resistant disease and validating FRα as an actionable target in ovarian cancer.
Key Limitations
Open-label design; FRα-high selection (~30–35% of platinum-resistant patients are FRα-high) limits population applicability; bevacizumab-naïve patients could receive bev-containing regimens (not tested here); FRα testing by PS2 assay not universally available; ocular toxicity (blurred vision, keratopathy) is class-specific and requires ophthalmology monitoring; mPFS benefit modest (5.6 vs 4.0 months) though OS benefit (3.7 months, HR 0.67) is more clinically meaningful; no BRCA/HRR stratification.
Clinical Context
FDA approved mirvetuximab soravtansine (Elahere) for FRα-positive, platinum-resistant epithelial ovarian/FT/PP carcinoma (after 1–3 prior regimens) in November 2022 based on the SORAYA single-arm trial, with MIRASOL (December 2023) confirming OS benefit and providing the evidence for full approval. MIRASOL is the first phase III ovarian cancer trial to show both PFS and OS benefit for an ADC in the platinum-resistant setting, transforming a subgroup (~30%) of platinum-resistant ovarian cancer into a targetable entity with a validated companion diagnostic (PS2 FRα IHC).