Clinical trialPhase 3Ovarian cancer

Mirvetuximab Soravtansine in FRα-Positive, Platinum-Resistant Ovarian Cancer

N Engl J Med · 2023453 patients

Moore KN, Angelergues A, Konecny GE, García Y, Banerjee S, Lorusso D, et al. N Engl J Med. 2023. 389:2162-2174

Study type: Clinical trial
Study name: MIRASOL (GOG-3045/ENGOT-ov55)
Phase: Phase 3
Design: Global, randomised, open-label, controlled confirmatory trial
Sample size: 453 patients
Source: N Engl J Med · 2023
Trial registration: NCT04209855

In plain words

Ovarian cancer that has become resistant to platinum drugs is hard to treat. Mirvetuximab is an "antibody-drug conjugate" that delivers an anticancer drug directly to cells that carry the folate receptor alpha. In patients whose tumour had high levels of this receptor, the drug helped people live longer than standard chemotherapy and had fewer serious side effects. Eye problems are common, and regular eye examinations are needed.

Key results

5.62 vs 3.98 months

Median progression-free survival

P<0.001

42.3% vs 15.9%

Objective response

Odds ratio 3.81 (95% CI 2.44–5.94); P<0.001

16.46 vs 12.75 months

Median overall survival

HR 0.67 (95% CI 0.50–0.89); P=0.005

Drugs in this study:Doxorubicin (Adriamycin)Paclitaxel (Taxol)

Dose and schedule cards

Mirvetuximab soravtansine (MIRASOL)

Platinum-resistant high-grade serous cancer with high FRα expression (75% or more of cells with 2+ intensity or higher); label: FRα-positive by an approved test, after 1 to 3 prior regimensCycle length: Every 21 daysOn the page “Ovarian cancer” · Platinum-resistant recurrence

Platinum-resistant high-grade serous cancer with high FRα expression (75% or more of cells with 2+ intensity or higher); label: FRα-positive by an approved test, after 1 to 3 prior regimens

Drug	Dose	Route	Schedule
Mirvetuximab soravtansine	6 mg/kg based on adjusted ideal body weight (AIBW)	IV, diluted only in 5% dextrose (incompatible with normal saline)	Day 1

Cycle length: Every 21 days
Duration: Until progression or unacceptable toxicity

Dose calculation: AIBW = IBW + 0.4 × (actual weight − IBW); IBW for women = 0.9 × height (cm) − 92. Premedication (at least 30 minutes before): dexamethasone 10 mg IV, diphenhydramine 25 to 50 mg and acetaminophen 325 to 650 mg, plus an antiemetic (5-HT3 antagonist). Eyes (boxed warning for visual impairment, keratopathy and dry eye): ophthalmic examination with visual acuity and slit-lamp examination before starting, every other cycle for the first 8 cycles and as needed; steroid eye drops, 1 drop in each eye 6 times daily from the day before the infusion until day 4, then 4 times daily on days 5 to 8 of each cycle; artificial tears at least 4 times daily. Grade 3–4 pneumonitis: permanently discontinue; monitor for peripheral neuropathy.

On the page “Ovarian cancer” · Platinum-resistant recurrence

Doses follow the trial protocol, guideline or official drug label (source given in the notes of each regimen). Before prescribing, check blood counts, renal and hepatic function, drug interactions and the patient’s condition, and adjust the dose according to the drug label.

Treatment arms and regimens

1Mirvetuximab soravtansine (227 patients)

Mirvetuximab soravtansine-gynx 6 mg/kg adjusted ideal body weight (AIBW), IV, on day 1 every 3 weeks.

2Investigator's choice chemotherapy (226 patients)

Paclitaxel 80 mg/m² IV (1-hour infusion) on days 1, 8, 15 and 22 every 4 weeks; or topotecan 4 mg/m² (30 minutes) on days 1, 8 and 15 every 4 weeks or 1.25 mg/m² on days 1 to 5 every 3 weeks; or pegylated liposomal doxorubicin 40 mg/m² (1 mg/min) on day 1 every 4 weeks.

Source of the regimen details: Abstract of the paper and ClinicalTrials.gov NCT04209855 (doses of the control-arm chemotherapy drugs)

Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.

Study population

Patients with platinum-resistant high-grade serous ovarian cancer who had received 1 to 3 prior lines of therapy and had high tumour FRα expression (75% or more of cells with staining intensity ‎2+‎ or higher).

Endpoints

Primary endpoint: investigator-assessed progression-free survival. Key secondary: objective response, overall survival and patient-reported outcomes.

Safety and side effects

Grade 3 or higher adverse events were less frequent with mirvetuximab than with chemotherapy (41.7% versus 54.1%), as were serious adverse events (23.9% versus 32.9%) and discontinuation due to adverse events (9.2% versus 15.9%). Ocular events (blurred vision, keratopathy) are the hallmark toxicity of this drug, and the FDA label has a boxed warning for ocular toxicity; ophthalmic examination and prophylactic eye drops are required.

Clinical significance and place in guidelines

The first treatment to improve overall survival in a phase 3 trial in platinum-resistant ovarian cancer. After accelerated approval in November 2022, the FDA granted full approval of mirvetuximab soravtansine in March 2024 for FRα-positive, platinum-resistant ovarian cancer after 1 to 3 lines of therapy. The ESMO Pan-Asian 2025 guideline recommends it as a treatment option for patients with FRα expression (75% or more at ‎2+‎ intensity) and platinum-resistant relapse after 1 to 3 lines of therapy [I, A]. FRα immunohistochemistry is a prerequisite for prescribing.

Limitations

Open-label design; only patients with high FRα expression were eligible, and the results cannot be applied to tumours with lower expression; there was no comparison with bevacizumab-containing regimens.

Original article (DOI)PubMed ClinicalTrials.gov

This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.