What is mirvetuximab soravtansine-gynx?
Mirvetuximab soravtansine-gynx is an antibody-drug conjugate that consists of three components: a folate receptor alpha (FR[alpha])-directed monoclonal antibody (IgG1 subtype), a small molecule anti-tubulin agent DM4, and a linker that covalently attaches DM4 to the mirvetuximab antibody. After binding to FR[alpha], mirvetuximab soravtansine-gynx is internalized and releases DM4 via proteolytic cleavage. This leads to microtubule network disruption within the cell and results in cell cycle arrest and apoptosis.
Mirvetuximab soravtansine-gynx is approved for the treatment of adult patients with FR[alpha] positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received 1-3 prior systemic treatment regimens.
Mirvetuximab soravtansine-gynx was granted accelerated FDA approval based on the single-arm, Phase II SORAYA study (J Clin Oncol 2023; doi: 10.1200/JCO.22.01900). This trial enrolled patients with platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. A total of 106 patients were enrolled with the median age being 62 years old. The confirmed overall response rate was 32.4 percent with 4.8 percent achieving a complete response and 27.6 percent achieving a partial response. The median duration of response was 6.9 months. The most common serious (Grades 3-4) adverse reactions were keratopathy (9%), blurred vision (6%), dry eye (2%), diarrhea (2%), and neutropenia (2%).
How do you administer this drug?
Mirvetuximab soravtansine-gynx is administered intravenously at 6 mg/kg once every 21 days based on adjusted ideal body weight (AIBW=ideal body weight (kg) + 0.4 x (actual weight [kg] - ideal body weight [kg]). The initial dose is administered at a rate of 1 mg/minute. If the 1 mg/minute rate is well-tolerated after 30 minutes, increase infusion rate to 3 mg/minute. If the 3 mg/minute rate is well-tolerated after 30 minutes, increase infusion rate to 5 mg/minute. If no infusion-related reactions occur with the previous dose, subsequent infusions should be started at the maximally tolerated rate and may be increased up to a maximum infusion rate of 5 mg/minute.
Are there any premedications needed for for this treatment?
Patients receiving mirvetuximab soravtansine-gynx should receive premedication prior to each dose to prevent infusion-related reactions. Premedication should include a corticosteroid (dexamethasone IV 10 mg), an antihistamine (diphenhydramine PO or IV 25 mg to 50 mg), and an antipyretic (acetaminophen PO or IV 325 mg to 650 mg) 30 minutes prior to each dose. Patients should receive an antiemetic (5HT3 serotonin receptor antagonist or alternative) prior to each dose and thereafter as needed for the prevention of chemotherapy-induced nausea and vomiting. Patients should also be instructed to administer ophthalmic topical steroids and lubricating eye drops starting the day prior to each infusion and continuing until Day 8 for prevention of ocular toxicity.
What are side effects associated with this drug (>=20%)?
Common adverse reactions include decreased serum albumin, decreased serum magnesium, abdominal pain, constipation, diarrhea, nausea, decreased hemoglobin, decreased neutrophils, leukopenia, lymphocytopenia, increased serum alanine aminotransferase, increased serum alkaline phosphatase, increased serum aspartate aminotransferase, fatigue, neuropathy, corneal disease, dry eye, and visual impairment.
What are uncommon side effects of this drug (<10%)?
Some uncommon but clinically relevant side effects include infusion-related reactions, pneumonitis, keratitis/keratopathy, and peripheral neuropathy.
Are there any important drug interactions?
No clinical trials have evaluated the drug interaction potential of mirvetuximab soravtansine-gynx. Strong CYP3A4 inhibitors may increase the serum concentration of the drug. Efgartigimod alfa may diminish the therapeutic effect of mirvetuximab soravtansine-gynx.
How do I adjust the dose in the setting of renal or hepatic insufficiency?
Dose adjustments are not required for renal insufficiency. However, effects of severe renal impairment and end-stage kidney disease on pharmacokinetics of mirvetuximab soravtansine-gynx have not been evaluated. Mirvetuximab soravtansine-gynx should be avoided in moderate-to-severe hepatic impairment (total bilirubin >1.5 times ULN).
What should my patients know about mirvetuximab soravtansine-gynx?
Patients who could become pregnant should use effective contraception during therapy and for 7 months after the last mirvetuximab soravtansine-gynx dose. Patients will require routine use of eye drops, as well as a baseline ophthalmic exam and every other cycle for the first 8 cycles and as clinically indicated. Topical steroids should only start after ophthalmic examination with a slit lamp.
* Ophthalmic topical steroids: Patients should instill 1 drop of topical steroids into each eye 6 times daily starting the day prior to each mirvetuximab soravtansine-gynx infusion and continue until Day 4. Patients can change to 1 drop into each eye 4 times daily for Days 5-8 of each mirvetuximab soravtansine-gynx cycle.
* Lubricating eye drops: Patients should administer lubricating eye drops at least 4 times daily and as needed during mirvetuximab soravtansine-gynx treatment.
What useful links are available?
* Highlights of prescribing information: https://bit.ly/3LVGKlY
Any ongoing clinical trials?
Mirvetuximab soravtansine-gynx is being studied in patients with endometrial cancer; breast cancer; and advanced-stage ovarian, fallopian tube, or primary peritoneal cancer. These trials are evaluating mirvetuximab soravtansine-gynx as monotherapy, as well as in combination with other chemotherapy agents.
LAUREN SPREEN, PHARMD, is PGY2 Oncology Resident at Barnes-Jewish Hospital in St. Louis, MO. JANELLE E. MANN, PHARMD, BCOP, is Clinical Oncology Pharmacist/Manager, Clinical Pharmacy Services at Washington University School of Medicine. She serves as the Pharmacy Forum column editor. RAMASWAMY GOVINDAN, MD, Professor of Medicine; Anheuser Busch Chair in Medical Oncology; Director, Section of Medical Oncology, Division of Oncology, Washington University School of Medicine, serves as the Pharmacy Forum column physician advisor.