Mirvetuximab soravtansine-gynx, a folate receptor alpha (FRα)-directed antibody conjugated with the microtuble inhibitor DM4, is an antineoplastic agent.1
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
Mirvetuximab soravtansine-gynx is used for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens.1, 3, 5, 6
The current indication for mirvetuximab soravtansine-gynx in the treatment of folate receptor-alpha positive, platinum-resistant ovarian cancer is based on two studies.1, 5, 6 The first study was a phase 3, open-label, randomized, active-controlled trial.1, 5 Adult patients ≥18 years of age were eligible for inclusion if they had a confirmed diagnosis of platinum-resistant, high-grade, serous ovarian cancer, received 1 to 3 previous lines of systemic therapy, and had disease progression while receiving or immediately after receiving the previous therapy.5 Patients were also required to have high FRα tumor expression as determined by the VENTANA FOLR1 (FOLR1-2.1) RxDx assay, at least one lesion that met the definition of measurable disease according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, and an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1.5 Patients were randomized to receive single-agent mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight) by IV infusion every 3 weeks or the investigator's choice of chemotherapy (i.e., paclitaxel 80 mg/m2every week within a 4 week cycle, pegylated liposomal doxorubicin 40 mg/m2 administered every 4 weeks, or topotecan 4 mg/m2 administered either on Days 1, 8, and 15 every 4 weeks or 1.25 mg/m2 for 5 consecutive days every 3 weeks).1, 5 Patients receiving mirvetuximab soravtansine-gynx were premedicated with acetaminophen or paracetamol, dexamethasone, and diphenhydramine.5 Prophylactic glucocorticoid eye drops were administered 6 times daily on days -1 to 4 and administered 4 times daily on days 5 to 8 of each treatment cycle; preservative-free lubricating artificial tears were recommended daily.1, 5 Patients receiving chemotherapy were premedicated at the investigator's discretion.1, 5
All patients received ocular examinations at screening.1, 5 Patients in the mirvetuximab soravtansine-gynx group had additional ocular examinations at the onset of ocular symptoms and at every other cycle thereafter.1, 5 Randomization was stratified according to the number of previous lines of therapy (1 to 3) and chemotherapy agent selected prior to randomization.1, 5 Patients were treated until disease progression, unacceptable toxicity, withdrawal of consent, or death.1, 5 Tumor assessments, including radiological assessments by computed tomography/magnetic resonance imaging scans were performed at screening and subsequently every 6 weeks from cycle 1 Day 1 for the first 36 weeks then every 12 weeks until disease progression, death, or the initiation of subsequent anticancer therapy, whichever occurred first.1, 3, 5 The primary end point was progression-free survival, defined as the time from the date of randomization until investigator-assessed progressive disease or death, whichever occurred first.1, 5 Secondary end points included confirmed complete or partial response and overall survival (defined as the time from the date of randomization until the date of death).1, 5
A total of 227 patients were assigned to the mirvetuximab soravtansine-gynx and 226 were assigned to the chemotherapy group (92 patients received paclitaxel, 81 patients received pegylated liposomal doxorubicin, and 53 patients received topotecan).5 The median age of patients in the mirvetuximab soravtansine-gynx group was 63 years and 66% were White.1, 5 Most patients had high-grade serous (100%) epithelial ovarian cancer (80.4%), had received 2 or 3 previous lines of therapy (86.1%), and had previous exposure to taxane (99.6%), bevacizumab (62%), and poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (55%).1, 5 Progression-free survival was longer in the mirvetuximab soravtansine-gynx group (median 5.6 months) than in the chemotherapy group (median 4 months).1, 5 Among the patients in the mirvetuximab soravtansine-gynx group, 5% had a complete response and 37% had a partial response, in comparison to 0% and 16%, respectively, in the chemotherapy group.1, 5 The median overall survival was 16.5 months in the mirvetuximab soravtansine-gynx group and 12.7 months in the chemotherapy group.1, 5
The second study was a single-arm, phase 2 study that evaluated the efficacy and safety of mirvetuximab soravtansine-gynx in patients with FRα-high, platinum-resistant, advanced, high-grade, serous ovarian cancer.1, 6 Female patients ≥18 years with confirmed diagnosis of high-grade, serous ovarian cancer, primary peritoneal cancer, or fallopian tube cancer were eligible for inclusion in the study.1, 6 Patients were required to have platinum-resistant disease and high FRα tumor expression based on the Ventant FOLR1 assay.1, 6 All patients had an ECOG performance status score of 0 or 1 and had received 1 to 3 previous lines of systemic anticancer therapy.1, 6 Patients received single-agent mirvetuximab soravtansine-gynx 6 mg/kg (based on adjusted ideal body weight), administered IV once every 3 weeks.1, 6 All patients received premedication with acetaminophen 325-650 mg, dexamethasone 10 mg IV, and diphenhydramine 25-50 mg orally or IV approximately 30 minutes prior to each infusion.3 An antiemetic medication was recommended before each dose of mirvetuximab soravtansine-gynx.3 Patients were mandated to use daily lubricating artificial tears and corticosteroid eye drops starting the day before receiving mirvetuximab soravtansine-gynx and continuing through day 8 of each cycle.6, 3 Patients received mirvetuximab soravtansine-gynx until progressive disease, unacceptable toxicity, withdrawal of consent, or death.1, 6 Tumor response assessments occurred every 6 weeks for the first 36 weeks and every 12 weeks thereafter.1, 6 The primary end point was objective response rate.1, 6 The secondary end point was duration of response (defined as the time from the initial complete or partial response until progressive disease).1, 6
A total of 106 patients were enrolled in the study and 104 patients were included in the final efficacy population.1 The median age of patients was 62 years and 96% of patients were White.1, 6 The percentage of patients with a primary diagnosis of epithelial ovarian, fallopian tube, and primary peritoneal cancer were 80%, 8% and 11 %, respectively.6 All patients had high-grade serous histology and 59% and 38% had stage III and stage IV disease at diagnosis, respectively.6 All patients received prior bevacizumab, 50% had received 3 prior lines of systemic therapy, and 47% of patients had received a prior PARP.1, 6 The observed overall response rate in this study was 32%; 5% of patients had a complete response and 27% had a partial response.1, 6 The median duration of response was 6.9 months.1, 6
The folate receptor plays a significant role in various processes involved in tumorigenesis.8 The FRα isoform, which is expressed in 80-96% of ovarian cancers, is a membrane-bound, glycosylphosphatidylinositol (GPI) anchor glycoprotein that is encoded by the FOLR1 gene.8 FRα is mostly present in cancers of the fallopian tubes and primary peritoneal cancers.8 Initial treatment for patients with advanced ovarian cancer is typically surgery and neoadjuvant chemotherapy with platinum-based doublet with or without bevacizumab therapy.3, 7 There are limited therapeutic options for patients with platinum-resistant ovarian cancer who have already received a bevacizumab-containing regimen.3 There are no other therapies approved for patents with ovarian cancer targeting FRα-expressing tumors.3 Mirvetuximab soravtansine-gynx provides a new treatment option for patients with FRα-expressing tumors; there is no other available therapies to date for patients with ovarian cancer targeting this biomarker.3
Dispensing and Administration Precautions
Mirvetuximab soravtansine-gynx is administered via IV infusion only.1 The drug is supplied in single-dose vials as a 5 mg/mL injection concentrate that must be further diluted prior to administration.1
Store mirvetuximab soravtansine-gynx vials upright in a refrigerator at 2 to 8ºC until the time of preparation in the original carton to protect from light.1 Do not freeze or shake.1
Administer the IV infusion using a 0.2 or 0.22 µm polyethersulfone (PES) in-line filter.1 Do not substitute other membrane materials.1
After the infusion is complete, flush the IV line with 5% dextrose injection to ensure delivery of the full dose.1 Do not use any other IV fluids.1
Administer premedications prior to mirvetuximab soravtansine-gynx administration (see Premedications under Dosage and Administration).1
Mirvetuximab soravtansine-gynx should be diluted with 5% dextrose injection prior to administration; the drug is incompatible with and should not be diluted with 0.9% sodium chloride injection.1 Do not mix with any other drugs or IV fluids.1
Dilute the commercially available injection concentrate with 5% dextrose injection to a final concentration of 1 to 2 mg/mL according to the following procedures.1
Calculate the dose (mg) based on patient's adjusted ideal body weight (AIBW), total volume (mL) of solution required, and the number of vials of mirvetuximab soravtansine-gynx needed.1 More than one vial will be needed for a full dose.1
Remove the vials from the refrigerator and allow to warm to room temperature.1 Inspect the vials visually for particulate matter and discoloration prior to administration.1 Mirvetuximab soravtansine-gynx is a clear to slightly opalescent, colorless solution.1 Gently swirl each vial prior to withdrawing the calculated dose volume of mirvetuximab soravtansine-gynx.1 Do not shake the vial.1
Using aseptic technique, withdraw the calculated dose volume of mirvetuximab soravtansine-gynx for subsequent dilution.1 Mirvetuximab soravtansine-gynx contains no preservatives and is intended for single-dose only.1 Discard any unused drug remaining in the vial.1
Determine the volume of 5% dextrose injection required to achieved the final diluted drug concentration.1 Either remove excess 5% dextrose injection from a prefilled IV bag or add the calculated volume of 5% dextrose injection to a sterile empty IV bag.1 Then add the calculated dose volume of mirvetuximab soravtansine-gynx to the IV bag.1 Gently mix the diluted drug solution by slowly inverting the bag several times.1 Do not shake or agitate.1
If the diluted infusion solution is not used immediately, store solution either at ambient temperature (18 to 25ºC) for no more than 8 hours (including infusion time), or under refrigeration at 2 to 8ºC for no more than 12 hours.1 If refrigerated, allow infusion bag to reach room temperature prior to administration.1 After refrigeration, administer the diluted infusion solution within 8 hours (including infusion time).1 Do not freeze prepared infusion solution.1
Administer the initial IV infusion at the rate of 1 mg/min.1 If well tolerated after 30 minutes at a rate of 1 mg/min, the infusion rate can be increased to 3 mg/min.1 If well tolerated after 30 minutes at a rate of 3 mg/min, the infusion rate can be increased to 5 mg/min.1
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/min, as tolerated.1
Administer the premedications in Table 1 prior to each infusion of mirvetuximab soravtansine-gynx to reduce the incidence and severity of infusion related reactions (IRRs), nausea, and vomiting.1
Premedication | Route of Administration | Examples (or equivalent) | Administration Time Prior to Mirvetuximab Soravtansine-gynx Infusion |
|---|---|---|---|
Antiemetic | Oral or IV | 5-HT3serotonin receptor antagonist or appropriate alternatives | Before each dose and thereafter as needed |
Antihistamine | Oral or IV | Diphenhydramine 25 mg to 50 mg | At least 30 minutes prior |
Antipyretic | Oral or IV | Acetaminophen 325 mg to 650 mg | At least 30 minutes prior |
Corticosteroid | IV | Dexamethasone 10 mg | At least 30 minutes prior |
Corticosteroid | Ophthalmic topical | Not provided | 1 drop in each eye 6 times daily starting the day prior to each infusion until day 4; then administer 1 drop in each eye 4 times daily for days 5-8 of each cycle of mirvetuximab soravtansine-gynx |
Consider additional premedications including corticosteroids the day prior to mirvetuximab soravtansine-gynx for patients who experienced IRRs.1
The use of lubricating eye drops is also recommended.1 Administer at least 4 times daily and as needed during treatment with mirvetuximab soravtansine-gynx.1 Patients should wait at least 10 minutes after ophthalmic topical steroid administration before instilling lubricating eye drops.1
Ovarian, Fallopian Tube, or Primary Peritoneal Cancer
The recommended initial dosage of mirvetuximab soravtansine-gynx for the treatment of adult patients with folate receptor-alpha positive, platinum-resistant, epithelial ovarian, fallopian tube, or primary peritoneal cancer, who have received 1 to 3 prior systemic treatment regimens is 6 mg/kg based on adjusted ideal body weight (AIBW) administered once every 3 weeks (21-day cycle) as an IV Infusion until disease progression or unacceptable toxicity.1 Dosing based on AIBW reduces exposure variability for patients who are either under or overweight.1
The total dose of mirvetuximab soravtansine-gynx is calculated based on a patient's AIBW using the following formula:1
AIBW=Ideal Body Weight (IBW [kg]) + 0.4*(Actual weight [kg]-IBW)1
Female IBW [kg]=0.9*height[cm]-921
Dosage Modifications for Toxicity
If adverse reactions occur, dosage modifications or temporary interruption of therapy may be required based on the severity of the reaction (see Table 2 and Table 3).1
Dose Reduction | Mirvetuximab Soravtansine-gynx Dose Level |
|---|---|
First Dose Reduction | 5 mg/kg adjusted ideal body weight (AIBW) once every 3 weeks (21-day cycle) |
Second Dose Reduction | 4 mg/kg AIBW once every 3 weeks (21-day cycle) Permanently discontinue in patients who cannot tolerate mirvetuximab soravtansine-gynx 4 mg/kg AIBW |
Adverse Reaction | Severity of Adverse Reaction | Dosage Modification |
|---|---|---|
Keratitis/Keratopathy | Nonconfluent superficial keratitis | Monitor |
Confluent superficial keratitis, a cornea epithelial defect, or ≥3-line loss in best corrected visual acuity | Withhold until improved or resolved, then maintain at same dose level or consider dose reduction | |
Corneal ulcer or stromal opacity or best corrected distance visual acuity 20/200 or worse | Withhold until improved or resolved, then reduce by one dose level (see Table 2) | |
Corneal perforation | Permanently discontinue | |
Uveitis | Grade 1/Rare cell in anterior chamber | Monitor |
Grade 2/1-2+ Cell or Flare in anterior chamber | Withhold until Grade 1 or less, then maintain dose at same dose level | |
Grade 3/3+ Cell or Flare in anterior chamber | Withhold until Grade 1 or less, then reduce dose by one dose level (see Table 2) | |
Grade 4/Hypopyon | Permanently discontinue | |
Pneumonitis | Grade 1 | Monitor |
Grade 2 | Withhold until Grade 1 or less, then maintain at same dose level or consider dose reduction (see Table 2) | |
Grade 3 or 4 | Permanently discontinue | |
Peripheral Neuropathy | Grade 2 | Withhold until Grade 1 or less, then reduce by one dose level (see Table 2) |
Grade 3 or 4 | Permanently discontinue | |
Infusion-Related Reactions/Hypersensitivity | Grade 1 | Maintain infusion rate |
Grade 2 | Interrupt infusion and administer supportive treatment After recovery from symptoms, resume the infusion at 50% of the previous rate, and if no further symptoms appear, increase rate as appropriate until infusion is completed Administer additional premedication for future cycles (see Dosage and Administration section) | |
Grade 3 or 4 | Immediately stop infusion and administer supportive treatment Advise patent to seek emergency treatment and immediately notify their healthcare provider if the infusion-related symptoms recur Permanently discontinue | |
Hematological | Grade 3 or 4 | Withhold until Grade 1 or less, then resume at one lower dose level (see Table 2) |
Other Adverse Reactions | Grade 3 | Withhold until Grade 1 or less, then resume at one lower dose level (see Table 2) |
Grade 4 | Permanently discontinue |
The manufacturer makes no specific dosage recommendations for patients with mild hepatic impairment.1, 3 Mirvetuximab soravtansine-gynx is not recommended in patients with moderate or severe hepatic impairment.1
The manufacturer makes no specific dosage recommendations for patients with mild to moderate renal impairment (Clcr≥ 30 mL/minute).1, 3 There are no data in patients with severe renal impairment (Clcr<30 mL/minute).1, 3
The manufacturer makes no specific dosage recommendations for geriatric patients.1
A boxed warning about the risk of ocular toxicity is included in the prescribing information for mirvetuximab soravtansine-gynx.1 Mirvetuximab soravtansine-gynx can cause severe ocular adverse reactions, including visual impairment, keratopathy (corneal disorders), dry eye, photophobia, eye pain, and uveitis.1
Ocular adverse reactions occurred in 59% of patients with ovarian cancer treated with mirvetuximab soravtansine-gynx.1 Among these patients, 11% experienced Grade 3 ocular adverse reactions, including blurred vision, keratopathy/keratitis (corneal disorders), dry eye, cataract, photophobia, and eye pain; two patients (0.3%) experienced Grade 4 events (keratopathy and cataract).1 The most common (≥5%) ocular adverse reactions were blurred vision (48%), keratopathy (36%), dry eye (27%), cataract (16%), photophobia (14%), and eye pain (10%).1
The median time to onset for first ocular adverse reaction was 5.1 weeks (range 0.1-68.6 weeks).1 Of the patients who experienced ocular events, 53% had complete resolution and 38% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up.1 Ocular adverse reactions led to permanent discontinuation of mirvetuximab soravtansine-gynx in 1% of patients.1
Premedication and use of lubricating and ophthalmic topical steroid eye drops during treatment with mirvetuximab soravtansine-gynx are recommended.1 Advise patients to avoid use of contact lenses during treatment with mirvetuximab soravtansine-gynx unless directed by a healthcare provider.1
Refer patients to an eye care professional for an ophthalmic exam including visual acuity and slit lamp exam prior to treatment initiation, every other cycle for the first 8 cycles, and as clinically indicated.1 Promptly refer patients to an eye care professional for any new or worsening ocular signs and symptoms.1
Monitor for ocular toxicity and withhold, reduce, or permanently discontinue mirvetuximab soravtansine-gynx based on severity and persistence of ocular adverse reactions.1
Other Warnings and Precautions
Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with mirvetuximab soravtansine-gynx.1
Pneumonitis occurred in 10% of patients treated with mirvetuximab soravtansine-gynx, including 1% with Grade 3 events, and 1 patient (0.1%) with a Grade 4 event.1 One patient (0.1%) died due to respiratory failure in the setting of pneumonitis and lung metastases and one patient died due to respiratory failure of unknown etiology.1 Pneumonitis led to permanent discontinuation of mirvetuximab soravtansine-gynx in 3% of patients.1
Monitor patients for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams.1 Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations.1 Withhold mirvetuximab soravtansine-gynx for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤Grade 1 and consider dose reduction.1 Permanently discontinue mirvetuximab soravtansine-gynx in all patients with Grade 3 or 4 pneumonitis.1 Patients who are asymptomatic may continue dosing of mirvetuximab soravtansine-gynx with close monitoring.1
Peripheral neuropathy occurred in 36% of patients with ovarian cancer treated with mirvetuximab soravtansine-gynx across clinical trials; 3% of patients experienced Grade 3 peripheral neuropathy.1 Peripheral neuropathy adverse reactions included peripheral neuropathy (20%), peripheral sensory neuropathy (9%), paraesthesia (6%), neurotoxicity (3%), hypoaesthesia (1%), peripheral motor neuropathy (0.9%), polyneuropathy (0.3%), and peripheral sensorimotor neuropathy (0.1%).1
The median time to onset of peripheral neuropathy was 5.9 weeks (range 0.1-26.7 weeks).1 Of the patients who experienced peripheral neuropathy, 23% had complete resolution and 12% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade) at last follow up.1 Peripheral neuropathy led to discontinuation of mirvetuximab soravtansine-gynx in 0.7% of patients.1
Monitor patients for signs and symptoms of neuropathy, such as paresthesia, tingling or a burning sensation, neuropathic pain, muscle weakness, or dysesthesia.1 For patients experiencing new or worsening peripheral neuropathy, withhold therapy, reduce the dosage, or permanently discontinue mirvetuximab soravtansine-gynx based on the severity.1
Based on its mechanism of action, mirvetuximab soravtansine-gynx can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.1
Advise pregnant women of the potential risk to a fetus.1 Advise females of reproductive potential to use effective contraception during treatment with mirvetuximab soravtansine-gynx and for 7 months after the last dose.1
Based on its mechanism of action, mirvetuximab soravtansine-gynx can cause embryo-fetal harm when administered to a pregnant woman because it contains a genotoxic compound (DM4) and affects actively dividing cells.1 Human immunoglobulin G (IgG) is known to cross the placental barrier; therefore, mirvetuximab soravtansine-gynx has the potential to be transmitted from the mother to the developing fetus.1 There are no available human data on mirvetuximab soravtansine-gynx use in pregnant women to inform a drug-associated risk.1 No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine-gynx.1 Advise patients of the potential risk to a fetus.1
No reproductive or developmental animal toxicity studies have been conducted with mirvetuximab soravtansine-gynx.1 The cytotoxic component of mirvetuximab soravtansine-gynx, DM4, disrupts microtubule function, is genotoxic, and can be toxic to actively dividing cells, suggesting it has the potential to cause embryotoxicity and teratogenicity.
There are no data on the presence of mirvetuximab soravtansine-gynx in human milk or the effects on the breastfed child or milk production.1 Because of the potential for serious adverse reactions in a breastfed child, advise women not to breastfeed during treatment with mirvetuximab soravtansine-gynx and for 1 month after the last dose.1
Females and Males of Reproductive Potential
Mirvetuximab soravtansine-gynx can cause embryo-fetal harm when administered to a pregnant woman.1
Verify pregnancy status in females of reproductive potential prior to initiating mirvetuximab soravtansine-gynx.1
Advise females of reproductive potential to use effective contraception during treatment with mirvetuximab soravtansine-gynx and for 7 months after the last dose.1
Safety and effectiveness of mirvetuximab soravtansine-gynx have not been established in pediatric patients.1
No clinically meaningful differences in efficacy or safety were observed between patients ≥65 years of age compared to younger patients.1
Population pharmacokinetic analysis indicates that age does not have a clinically meaningful effect on the pharmacokinetics of mirvetuximab soravtansine-gynx.1
Avoid use of mirvetuximab soravtansine-gynx in patients with moderate or severe hepatic impairment (total bilirubin >1.5 ULN).1
No dosage adjustment of mirvetuximab soravtansine-gynx is recommended for patients with mild hepatic impairment (total bilirubin ≤ULN and AST >ULN or total bilirubin >1 to 1.5 times ULN and any AST).1
No dosage adjustment of mirvetuximab soravtansine-gynx is recommended for patients with mild to moderate renal impairment (Clcr30 to 90 mL/minute).1 The effect of severe renal impairment (Clcr15 to < 30 mL/minute) or end-stage renal disease on mirvetuximab soravtansine-gynx is unknown.1
The most common (≥20%) adverse reactions, including laboratory abnormalities, reported with mirvetuximab soravtansine-gynx in clinical studies were vision impairment, fatigue, increased aspartate aminotransferase, nausea, increased alanine aminotransferase, keratopathy, abdominal pain, decreased lymphocytes, peripheral neuropathy, diarrhea, decreased albumin, constipation, increased alkaline phosphatase, dry eye, decreased magnesium, decreased leukocytes, decreased neutrophils, and decreased hemoglobin.1
Drug-drug interaction studies with mirvetuximab soravtansine-gynx have not been performed.1, 3 Unconjugated DM4 and its S-methyl-DM4 metabolite undergo metabolism by cytochrome P-450 (CYP) 3A4.3 DM4 and S-methyl DM4 have not been shown to directly inhibit cytochrome P-450 (CYP)1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, or CYP3A4/5.3 Unconjugated DM4 exhibits time-dependent inhibition of CYP3A4.1, 3 S-methyl DM4 has demonstrated weak time-dependent inhibition of CYP2C8 and CYP2C9.3 DM4 and S-methyl-DM4 do not induce CYP1A2, CYP2B6, or CYP3A4.1, 3
Unconjugated DM4 and S-methyl DM4 are substrates, but not inhibitors, of P-gp.1, 3 DM4 and S-methyl DM4 are substrates, but not inhibitors, of multidrug resistance 1 (MDR1).3
Drugs Affecting or Metabolized by Hepatic Microsomal Enzymes
Strong CYP3A4 inhibitors: Concomitant use of mirvetuximab soravtansine-gynx with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure, which may increase the risk of adverse reactions.1, 3 Closely monitor for mirvetuximab soravtansine-gynx adverse reactions.1, 3
Mirvetuximab soravtansine-gynx is an antibody-drug conjugate consisting of a humanized immunoglobulin G1 antibody directed against folate receptor alpha (FRα) attached to a microtuble inhibitor (DM4) via a cleavable linker.1, 3 Each antibody is conjugated to an average of 3 to 4 molecules of DM4.3 FRα plays a critical role in cellular uptake of folate and is upregulated on the surface of many epithelial-derived tumors.3 Upon binding to FRα, mirvetuximab soravtansine-gynx is internalized and DM4 is released intracellularly via proteolytic cleavage.1 DM4 inhibits tubulin polymerization and microtubule assembly within the cell, resulting in cell cycle arrest and apoptotic cell death.1, 3
Peak mirvetuximab soravtansine-gynx concentrations were observed near the end of IV infusion.1 Peak unconjugated DM4 and S-methyl-DM4 concentrations were observed on the second day and third day after administration, respectively.1 Steady state concentration of mirvetuximab soravtansine-gynx, DM4, and S-methyl-DM4 are reached after one 3-week cycle.1 Plasma protein binding of DM4 and S-methyl DM4 are >99%.1, 3 The half-life of mirvetuximab soravtansine-gynx after the first dose is 4.8 days.1, 3 The half-life of unconjugated DM4 and S-methyl-DM4 are 2.8 and 5 days, respectively.1 The monoclonal antibody portion of mirvetuximab soravtansine-gynx is expected to be metabolized into small peptides by catabolic pathways.1 Unconjugated DM4 and S-methyl-DM4 undergo metabolism by cytochrome P-450 (CYP)3A4.1, 3 Biliary excretion is the primary route of elimination for DM4.3 Urinary excretion accounts for approximately 0.7% of the mirvetuximab soravtansine-gynx dose.3
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care. For further information on the handling of antineoplastic agents, see the ASHP Guidelines on Handling Hazardous Drugs at [Web].
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
Mirvetuximab soravtansine-gynx is obtained through designated specialty pharmacies.4 Contact manufacturer or consult the website ([Web]) for specific availability information. 4
Routes | Dosage Forms | Strengths | Brand Names | Manufacturer |
|---|---|---|---|---|
Parenteral | Injection concentrate, for IV infusion | 5 mg/mL | Elahere® | ImmunoGen |
AHFS® Drug Information. © Copyright, 1959-2026, Selected Revisions June 10, 2025. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, MD 20814.
Only references cited for selected revisions after 1984 are available electronically.
1. ImmunoGen, Inc. ELAHERE® (mirvetuximab soravtansine) INTRAVENOUS prescribing information. North Chicago, IL; 2024 Oct.
2. NIOSH list of hazardous drugs in healthcare settings, U.S. Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2025-103. Accessed 2025 Mar 7. Updates may be available at National Institute for Occupational Safety and Health (NIOSH) website.
3. Center for Drug Evaluation and Research. Multi-Discipline Review. Revised 2018 Oct. From FDA website.
4. ImmunoGen. Ordering Information. From Elahere website. Accessed 2025 Mar 05.
5. Moore KN, Angelergues A, Konecny GE, Garcia Y, Banerjee S, Lorusso D et al. Mirvetuximab soravtansine in FRα-positive, platinum-resistant ovarian cancer. N Engl J Med 2023;389:2162-74.
6. Matulonis UA, Lorusso D, Oaknin A, Pignata S, Dean A, Denys H e tal. Efficacy and safety of mirvetuximab soravtansine in patients with platinum-resistant ovarian cancer with high folate receptor alpha expression: Results from the SORAYA study. J Clin Oncol 2023;41:2436-45.
7. American Cancer Society. Cancer Facts & Figures 2022.Atlanta: American Cancer Society; 2022.
8. Gonzalez T, Muminovic M, Nano O, Vulfovich M. Folate receptor alpha-a novel approach to cancer therapy. Int J Mol Sci 2024;25:1046.
9. Institute for Safe Medication Practices. ISMP list of high-alert medications in acute care settings. [Web]