Mirvetuximab Soravtansine-Gynx - Targeting Hope in FRα Positive, Platinum-Resistant Cancers

Overview

The medication known as Mirvetuximab soravtansine-gynx is used to treat folate receptor alpha positive (FRα), platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancers. It functions by focusing on particular proteins in cancer cells to inhibit their growth. The United States Food and Drug Administration (USFDA) approved Mirvetuximab soravtansine-gynx on November 14, 2022.

Drug Group:

Mirvetuximab soravtansine-gynx belongs to a category of drugs known as folate receptor alpha-directed antibodies and microtubule inhibitor conjugates.

Indications:

Adult patients with folate receptor-alpha (FRα) positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer can be treated with Mirvetuximab soravtansine-gynx. These patients have already tried between one and three different therapies. Physicians select individuals for this treatment according to a certain test (presence of FRα tumor expression) that has FDA approval.

Contraindications:

None.

Dosage Forms and Available Strengths:

Injection: This medication is supplied as a single-dose vial holding a colorless, clear-to-hazy liquid. Five milligrams (mg) of the medication are included in each milliliter (mL) of the solution.

For Patients

What Is FRα Positive, Platinum-Resistant Epithelial Ovarian, Fallopian Tube, or Primary Peritoneal Cancer?

A type of cancer that affects the ovaries, fallopian tubes, or peritoneum (the lining of the abdomen) is called FRα positive, platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer. When a cancer cell is FRα positive, it means that it has folate receptor alpha, a protein that is present on its surface. When ovarian cancer is treated with platinum-based chemotherapy, the cancer is said to be platinum-resistant if it does not react well to the treatment. As this particular cancer is more aggressive and challenging to treat, it is not responsive to typical chemotherapy methods.

What Are the Clinical Uses of Mirvetuximab Soravtansine-Gynx?

For patients who have previously undergone chemotherapy but have not responded to the treatment, Mirvetuximab soravtansine-gynx injection is a medication used to treat certain types of ovarian, fallopian tube, and peritoneal cancer. It is part of a class of drugs that both target and alter the structure of a certain protein found in cancer cells. This medication functions by directly killing cancer cells.

How Should Mirvetuximab Soravtansine-Gynx Be Used?

Mirvetuximab soravtansine-gynx injection is administered intravenously (into a vein) by a physician or nurse at a clinic or hospital. It is supplied as a solution (liquid). It is often administered once every three weeks. The physician will determine the number of cycles to be received. Precautionary measures against infusion-related reactions, nausea, and vomiting shall be given before each infusion of Mirvetuximab soravtansine-gynx. If any side effects are encountered, the physician or nurse will monitor throughout the infusion and may modify the infusion rate or dose of the current infusion or any subsequent infusion.

What Are the Side Effects of Mirvetuximab Soravtansine-Gynx?

Side effects are possible with Mirvetuximab soravtansine-gynx injection. If a patient experiences any of these symptoms, they should let the doctor know if they are bothersome or persistent:

• Sickness.

• Pain in the abdomen.

• Tiredness.

• Constipation.

• Vomiting.

• Weakness or spasms in the muscles.

Certain adverse effects may be dangerous. Patients should call the doctor right away or seek emergency medical attention if they experience any of the following symptoms,

• New or worsening numbness or tingling in the feet or hands or weakening in the muscles.

• Breathing difficulties.

• Coughing.

• Shortness of breath.

• Chest pain.

Injections of Mirvetuximab soravtansine-gynx may also have other adverse effects. If a patient experiences any odd issues while using this drug, they should contact the physician.

What Are the Things to Inform the Doctor Before Taking Mirvetuximab Soravtansine-Gynx?

Patients are recommended to disclose any allergies to this medication or any of its constituents to the doctor and pharmacist before obtaining an injection of Mirvetuximab soravtansine-gynx. They should also list all vitamins, minerals, herbal products, and medications that they have taken or plan to take. Doses may need to be changed, and the patient will need to be constantly watched for any possible side effects.

Patients with a history of kidney dysfunction or liver functioning difficulties, as well as vision or eye problems, should let the doctor know. Patients who are contemplating a pregnancy should talk to the doctor about it. It is important to refrain from getting pregnant while on Mirvetuximab soravtansine-gynx injection and for a minimum of seven months following the final dosage. Using reliable birth control is crucial during treatment, and it is advised to see a doctor if one becomes pregnant because this medication may harm the unborn child.

Patients must let the doctor know if they are nursing or intend to start breastfeeding. Breastfeeding should be avoided while taking the injection of Mirvetuximab soravtansine-gynx and for at least one month following the final dosage.

Dietary Consideration: Maintain the same diet unless advised otherwise by the doctor.

Missed Dose: Make sure to contact the physician right away if one is unable to keep the scheduled injection appointment for Mirvetuximab soravtansine-gynx.

For Doctors

Pharmacodynamics:

• Relationships Between Exposure and Response: Individuals who received higher doses of Mirvetuximab soravtansine-gynx often showed better response rates. However, the likelihood of developing peripheral neuropathy and grade II vision impairments rose with more medication exposure.

• Cardiac Electrophysiology: The QTc interval (a parameter assessing cardiac rhythm) was not significantly altered by Mirvetuximab soravtansine-gynx at the standard dosage that physicians advised.

Mechanism of Action:

An antibody-drug conjugate (ADC) is a class of therapy that includes Mirvetuximab soravtansine-gynx. This medication consists of two components: a tiny chemical known as DM4 and an antibody. The chimeric IgG1 antibody specifically targets the folate receptor alpha (FRα) protein, which is present in cancer cells. The DM4 molecule functions as a microtubule inhibitor and is linked to the antibody by a breakable linker. The DM4 molecule is released from the cancer cells when the antibody attaches to FRα on the cells. The cancer cells' microtubule network is then disrupted by DM4, which halts the growth of the cells and causes apoptosis (the mechanism by which cells die).

Pharmacokinetics:

Pharmacokinetics examines how medications flow through the body. In order to study Mirvetuximab soravtansine-gynx, individuals were given varying doses, and the plasma levels were measured.

• Exposure: The highest plasma levels of Mirvetuximab soravtansine-gynx were observed during the infusion after patients received the prescribed dose of six mg/kg (milligrams per kilogram) adjusted ideal body weight (AIBW). Later on, around the second and third days, the largest concentrations of its breakdown products, unconjugated DM4 and S-methyl-DM4, were detected. The amounts of these drugs reached a stable state after one treatment cycle, and continued doses only slightly increased it.

• Distribution: The body distributes Mirvetuximab soravtansine-gynx, which has an average volume comparable to a few large soda bottles. The majority of the breakdown products, S-methyl DM4 and DM4, are attached to blood proteins.

• Elimination: Mirvetuximab soravtansine-gynx and the byproducts of its breakdown are progressively eliminated by the body through the kidneys. It takes about 4.8 days for Mirvetuximab soravtansine-gynx, 2.8 days for DM4, and 5.0 days for S-methyl-DM4 for half of the medicine to be eliminated from the body.

• Metabolism: The body breaks down Mirvetuximab soravtansine-gynx into smaller pieces, whereas CYP3A4 is responsible for processing DM4 and S-methyl-DM4. Although they make up a minor portion of the overall drug levels in the blood, these breakdown products are the principal forms present.

• Excretion: Within 24 hours of infusion, the breakdown product S-methyl-DM4 and another metabolite were discovered in urine, indicating that the body primarily excretes them through urine.

What Is the Dosage and Method of Administration For Mirvetuximab Soravtansine-Gynx?

• Selection of Patients: As suggested for platinum-resistant epithelial ovarian, fallopian tube, or primary peritoneal cancer, patients should be chosen for Mirvetuximab soravtansine-gynx treatment based on the presence of FRα tumor expression.

• Recommended Dosage: The recommended intravenous infusion dose of Mirvetuximab soravtansine-gynx is six mg/kg adjusted ideal body weight (AIBW), administered once every three weeks (21-day cycle) until the condition progresses or the level of toxicity is unacceptable.

• Prescription Drugs and Necessary Eye Care:

  • Premedications should be given to patients before each Mirvetuximab soravtansine-gynx infusion in order to lower the frequency and intensity of infusion-related reactions (IRRs), nausea, and vomiting. Corticosteroids, antihistamines, antipyretics, and antiemetics are among them. Assessments of the eyes, such as slit lamp and visual acuity tests, should be performed before starting therapy, every other cycle during the first eight cycles, and as directed by a physician. It is important to use lubricating eye drops and ophthalmic topical steroids according to prescription.

  • When taking Mirvetuximab soravtansine-gynx, dosage changes entail cutting back or stopping the medication in response to unfavorable side effects. The beginning dose is six mg/kg AIBW; if necessary, this can be reduced to five mg/kg and eventually four mg/kg. Patients who are unable to tolerate the lowest dose should be permanently removed from treatment. Depending on the severity of the reaction, different dosage adjustments are made to address adverse reactions such as keratitis or keratopathy, uveitis, pneumonitis, peripheral neuropathy, infusion-related reactions or hypersensitivity, and other adverse reactions. These adjustments may include holding, reducing, or permanently stopping treatment. With these adjustments, the goal is to minimize side effects while maximizing treatment effectiveness and keeping a regular three-week gap between doses.

• Preparation:

  • Mirvetuximab soravtansine-gynx is a potent medication. Handle and dispose of it with caution.

  • Determine the appropriate dosage of Mirvetuximab soravtansine-gynx by using the patient's weight as a guide. For the full dosage, more than one vial might be required.

  • Before using, let the Mirvetuximab soravtansine-gynx vial reach room temperature.

  • Before using, check the vials for any particles or color changes. It should appear clear to see.

  • Make sure to twist each vial gently before removing the appropriate amount.

  • Use hygienic methods to extract the appropriate quantity of Mirvetuximab soravtansine-gynx. It is best to throw away any remaining medication.

• Dilution:

  • Combine Mirvetuximab soravtansine-gynx with five percent Dextrose Injection, USP (United States Pharmacopeia), a particular kind of fluid.

  • Avoid combining Mirvetuximab soravtansine-gynx with other medications or liquids.

  • Calculate how much five percent USP Dextrose Injection is required to combine with Mirvetuximab soravtansine-gynx.

  • Gently turn the bag to gradually combine the diluted medication. Do not shake it.

  • The mixture can be kept for a brief period at room temperature or in the refrigerator if it is not used right away. Make sure to utilize it within the allotted time.

• Administration:

  • Before giving the patient the medication, check the bag for any particles or color changes.

  • Before giving Mirvetuximab soravtansine-gynx, administer any pre-medications that have been prescribed.

  • Only inject Mirvetuximab soravtansine-gynx intravenously and through a using a 0.2 or 0.22 µm (micrometer) polyethersulfone (PES) in-line filter.

  • If the patient tolerates the infusion rate well, start slowly and raise it gradually.

  • Use five percent Dextrose Injection, USP, to flush the intravenous line following the infusion. Avoid using any other liquids.

Storage and Handling:

When it is time to prepare, keep Mirvetuximab soravtansine-gynx vials upright in the original carton and refrigerate between two degrees Celsius and eight degrees Celsius (36 degrees Fahrenheit and 46 degrees Fahrenheit). Keep them away from light. Avoid shaking or freezing.

Clinical Studies:

The efficacy of Mirvetuximab soravtansine-gynx was investigated in a trial comprising 106 individuals with a particular kind of ovarian cancer. Several therapies, including Bevacizumab, had already been administered to these patients. Every three weeks, an IV infusion of Mirvetuximab soravtansine-gynx was administered until the cancer either spread or the adverse effects were intolerable. The investigation discovered that:

• Of the patients treated with Mirvetuximab soravtansine-gynx, about 32 percent had an overall response; of these, about five percent had a complete reaction, and 27 percent had a partial response.

• The typical response time for individuals who replied to Mirvetuximab soravtansine-gynx was roughly 6.9 months.

According to these results, patients who may have run out of other therapy options now have hope because Mirvetuximab soravtansine-gynx has proven to be beneficial in treating platinum-resistant ovarian cancer.

Drug Interactions:

Strong CYP3A4 Inhibitors: The compound DM4 found in Mirvetuximab soravtansine-gynx is impacted by the liver enzyme CYP3A4. Taking drugs that potently block CYP3A4 may cause the body's levels of DM4 to rise. This may increase the possibility of having negative reactions to Mirvetuximab soravtansine-gynx. When using Mirvetuximab soravtansine-gynx in conjunction with potent CYP3A4 inhibitors, it is critical to keep a close eye on patients in case of any adverse effects.

Warnings and Precautions:

• Ocular Abnormalities: There is a chance that receiving Mirvetuximab soravtansine-gynx treatment could result in serious eye issues such as uveitis, dry eyes, photophobia, corneal abnormalities, and vision impairment. These side effects affected about 61 percent of individuals with ovarian cancer, with nine percent being categorized as severe (Grade 3). It is important to get regular eye exams and to report any new or worsening symptoms as soon as possible.

• Pneumonitis: 10 percent of individuals receiving Mirvetuximab soravtansine-gynx experienced pneumonia, a potentially fatal lung ailment. Hypoxia, coughing, dyspnea, and abnormal radiological exam results are possible symptoms. To properly manage this illness, it is imperative to monitor for signs and take early action when necessary.

• Peripheral Neuropathy: After receiving Mirvetuximab soravtansine-gynx therapy, 36 percent of patients developed peripheral neuropathy, with two percent having severe cases. Tingling, burning feelings, weakness, or discomfort in the limbs are possible symptoms. To address this negative effect, effective management measures and close monitoring are required.

• Embryo-Fetal Toxicity: Taking Mirvetuximab soravtansine-gynx during pregnancy carries a risk of harming the fetus. To minimize any harm to the fetus, effective contraception is indicated during therapy and for a brief period following the final dose. Healthcare professionals should counsel patients on adequate contraception and address these dangers.

Use in Specific Populations:

• Pregnancy: Because Mirvetuximab soravtansine-gynx contains a substance that might influence the growing fetus's cells, taking it while pregnant could harm the unborn child. There is no particular data on its effects on pregnant women, nevertheless. It is crucial to talk about possible dangers with the physician if one intends to get pregnant while taking Mirvetuximab soravtansine-gynx.

• Lactation: No information is available regarding the effects of Mirvetuximab soravtansine-gynx on the nursing infant or whether it enters breast milk. It is recommended not to breastfeed during Mirvetuximab soravtansine-gynx treatment and for one month following the last dose due to the possibility of injury.

• Reproductive Potential: Before beginning therapy, it is important to determine whether or not a fetus is developing because Mirvetuximab soravtansine-gynx can harm developing fetuses. Effective contraception should be used by women who are fertile both during the Mirvetuximab soravtansine-gynx treatment and for seven months following the last dosage.

• Pediatric Use: There is no proof of Mirvetuximab soravtansine-gynx’s safety or efficacy in kids.

• Geriatric Use: Research indicates that Mirvetuximab soravtansine-gynx’s safety and efficacy are not greatly impacted by age. The results for older and younger individuals did not significantly differ from one another.

• Renal Impairment: Patients with mild to severe renal impairment do not require a dosage change. Severe renal failure and its consequences are uncertain.

• Hepatic Impairment: Patients with mild to moderate liver disease should not use Mirvetuximab soravtansine-gynx. However, dosage adjustments are not required for people with moderate liver problems.