Elahere · 4.8 Undesirable effects · 1

HOS-099107 · has-adverse-reaction-information · PDF-Seite 9

Summary of safety profile The most common adverse reactions with mirvetuximab soravtansine were blurred vision (43%), nausea (41%), diarrhoea (39%), fatigue (35%), abdominal pain (30%), keratopathy (29%), dry eye (27%), constipation (26%), vomiting (23%), decreased appetite (22%), peripheral neuropathy (20%), headache (19%), asthenia (18%), AST increased (16%), and arthralgia (16%). The most commonly reported serious adverse reactions were pneumonitis (4%), small intestinal obstruction (3%), intestinal obstruction (3%), pleural effusion (2%), abdominal pain (2%), dehydration (1%), constipation (1%), nausea (1%), ascites (1%) and thrombocytopenia (<1%). Adverse reactions that most commonly led to dose reduction or dose delay were blurred vision (17%), keratopathy (10%), dry eye (5%), neutropenia (5%), keratitis (4%), cataract (3%), visual acuity reduced (3%), thrombocytopenia (3%), peripheral neuropathy (3%), and pneumonitis (3%). Permanent discontinuation due to an adverse reaction occurred in 12% of patients who received mirvetuximab soravtansine, including most commonly, gastrointestinal disorders (4%), respiratory, thoracic, and mediastinal disorders (3%), blood and lymphatic system disorders (1%), nervous system disorders (1%), and eye disorders (1%). Tabulated list of adverse reactions The frequencies of adverse reactions are based on pooled data from 4 clinical studies which included 682 patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer (collectively referenced as Epithelial Ovarian Cancer (EOC) treated with mirvetuximab soravtansine 6 mg/kg AIBW administered once every 3 weeks. The median duration of treatment with mirvetuximab soravtansine was 19.1 weeks (range: 3, 132 weeks). The adverse reaction frequencies from clinical studies are based on all-cause adverse event frequencies, for which, after thorough assessment, a causal relationship between the medicinal product and the adverse event is at least a reasonable possibility. Frequencies are defined as: very common (≥1/10); common (≥1/100 to <1/10); uncommon (≥1/1 000 to <1/100); rare (≥1/10 000 to <1/1 000); very rare (<1/10 000). Within each frequency grouping, where relevant, adverse reactions are presented in order of decreasing seriousness. Table 4: Tabulated list of all grade adverse reactions in patients treated with mirvetuximab soravtansine in clinical studies System Organ Class Frequency category Adverse reac

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HOS-099103 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1.

HOS-099102 · has-indication-information · PDF-Seite 2

ELAHERE as monotherapy is indicated for the treatment of adult patients with folate receptor-alpha (FRα) positive, platinum-resistant high grade serous epithelial ovarian, fallopian tube, or primary peritoneal cancer who have received one to three prior systemic treatment regimens (see section 4.2).

HOS-099105 · has-interaction-information · PDF-Seite 8

Clinical drug-drug interaction studies with ELAHERE have not been conducted. DM4 is a CYP3A4 substrate. Concomitant use of ELAHERE with strong CYP3A4 inhibitors may increase unconjugated DM4 exposure (see section 5.2), which may increase the risk of ELAHERE adverse reactions (see section 4.8). If concomitant use with strong CYP3A4 inhibitors (e.g. ceritinib, clarithromycin, cobicistat, idelalisib, itraconazole, ketoconazole, nefazodone, posaconazole, ritonavir, telithromycin, voriconazole) cannot be avoided, patients should be closely monitored for adverse reactions. Strong CYP3A4 inducers (e.g., phenytoin, rifampicin, carbamazepine) may decrease the exposure of unconjugated DM4.

HOS-099106 · has-pregnancy-information · PDF-Seite 8

Women of childbearing potential/Contraception The pregnancy status in patients of childbearing potential should be verified prior to initiating mirvetuximab soravtansine treatment. Patients of childbearing potential should use effective contraception during treatment with mirvetuximab soravtansine and for 7 months after the last dose. Pregnancy Based on its mechanism of action, mirvetuximab soravtansine can cause embryo-foetal harm when administered to a pregnant patient because it contains a genotoxic compound (DM4) and affects actively dividing cells (see sections 5.1 and 5.3). Human immunoglobulin G (IgG) is known to cross the placental barrier; therefore, mirvetuximab soravtansine has the potential to be transmitted from the pregnant patient to the developing foetus. There are no available human data on mirvetuximab soravtansine use in pregnant patients to inform a drug-associated risk. No reproductive or developmental animal toxicity studies were conducted with mirvetuximab soravtansine. Administration of ELAHERE to pregnant patients is not recommended, and patients should be informed of the potential risks to the foetus if they become or wish to become pregnant. Patients who become pregnant must immediately contact their doctor. If a patient becomes pregnant during treatment with ELAHERE or within 7 months following the last dose, close monitoring is recommended. Breast-feeding It is unknown whether mirvetuximab soravtansine/metabolites are excreted in human milk. A risk to the newborn/infant cannot be excluded as human immunoglobulin G (IgG) is known to pass on in breast milk. ELAHERE should not be used during breast-feeding and for 1 month after the last dose. Fertility Fertility studies have not been conducted with mirvetuximab soravtansine or DM4. There are no data on the effect of ELAHERE on human fertility. However, given the mechanism of action of ELAHERE leads to microtubule disruption and death of rapidly dividing cells, there is the potential for drug- related fertility effects.

HOS-099104 · has-warning-information · PDF-Seite 6

Traceability In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded. Ocular disorders Mirvetuximab soravtansine can cause severe ocular adverse reactions, including visual impairment (predominantly blurred vision), keratopathy (corneal disorders), dry eye, photophobia, and eye pain (see sections 4.7 and 4.8). Patients should be referred to an eye care professional for an ophthalmic exam before initiation of mirvetuximab soravtansine. Before the start of each cycle, the patient should be advised to report any new or worsening ocular symptoms to the treating physician or qualified individual. If ocular symptoms develop, an ophthalmic exam should be conducted, the patient’s ophthalmic report should be reviewed and the dose of mirvetuximab soravtansine may be modified based on the severity of the findings (see section 4.2). 6 Use of lubricating eye drops during treatment with mirvetuximab soravtansine is recommended. In patients who develop Grade 2 corneal adverse reactions, ophthalmic topical steroids are recommended for subsequent cycles of mirvetuximab soravtansine (see section 4.2). The physician should monitor patients for ocular toxicity and withhold, reduce, or permanently discontinue mirvetuximab soravtansine based on the severity and persistence of ocular adverse reactions (see section 4.2). Patients should be advised to avoid use of contact lenses during treatment with mirvetuximab soravtansine unless directed by a healthcare professional. Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD), including pneumonitis, can occur in patients treated with mirvetuximab soravtansine (see section 4.8). Patients should be monitored for pulmonary signs and symptoms of pneumonitis, which may include hypoxia, cough, dyspnoea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded through appropriate investigations. Mirvetuximab soravtansine treatment should be withheld for patients who develop persistent or recurrent Grade 2 pneumonitis until symptoms resolve to ≤Grade 1 and dose reduction should be considered. Mirvetuximab soravtansine should be permanently discontinued in all patients with Grade 3 or 4 pneumonitis (see section 4.2). Patients who are asymptomatic may continue dosing of mirvetuximab

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