Datroway

HOS-100999 · has-adverse-reaction-information · PDF-Seite 8

Summary of safety profile The pooled safety profile has been assessed from four clinical studies involving 841 patients who received Datroway 6 mg/kg body weight for the treatment of breast cancer. The median exposure to Datroway in this data set was 6.4 months (range 0.7 to 38 months). The most common adverse reactions were stomatitis (64.3%), nausea (52.7%), fatigue (40.4%), alopecia (36.9%), constipation (34.7%), vomiting (25.0%), dry eye (23.9%), anaemia (19.3%), decreased appetite (17.6%), keratitis (16.6%), aspartate aminotransferase (AST) increased (15.7%), rash (15.2%), neutropenia (14.9%), COVID-19 (13.1%), leukopenia (12.5%), alanine aminotransferase (ALT) increased (11.9%) and diarrhoea (10.2%). The most common Grade 3/4 adverse reactions were stomatitis (8.1%), amylase increased (3.9%), fatigue (3.8%), anaemia (3.0%), AST increased (1.9%), pneumonia (1.9%), keratitis (1.8%), neutropenia (1.8%), vomiting (1.7%), ALT increased (1.3%), nausea (1.1%) and urinary tract infection (1.1%). Grade 5 adverse reactions occurred in 0.5% of patients and were due to ILD/pneumonitis, dyspnoea and sepsis. The most common serious adverse reactions were pneumonia (1.9%), COVID-19 (1.5%), ILD/pneumonitis (1.1%) and vomiting (1.1%). The frequency of treatment discontinuation due to adverse reactions was 3.6%. The most common adverse reaction leading to treatment discontinuation was ILD/pneumonitis (1.7%). The frequency of dose reductions due to adverse reactions was 22.1%. The most common adverse reactions leading to dose reduction were stomatitis (11.5%), fatigue (3.4%), keratitis (1.8%), nausea (1.4%) and amylase increased (1.3%). The frequency of dose interruptions due to adverse reactions was 22.7%. The most common adverse reactions leading to dose interruption were stomatitis (5.0%), COVID-19 (3.8%), pneumonia (2.0%), keratitis (1.7%), fatigue (1.8%), amylase increased (1.8%), ILD/pneumonitis (1.5%), dry eye (1.2%), neutropenia (1.2%) and infusion-related reaction (1.2%). Tabulated list of adverse reactions Table 3 presents adverse reactions reported with Datroway. Adverse reactions are listed by System Organ Class and frequency category. The adverse reaction frequencies are based on all-cause adverse event frequencies, where a proportion of the events for an adverse reaction may have other causes than datopotamab deruxtecan, such as the disease, other medicinal products or unrelated causes. The severity of adverse drug reactions was assessed based on t

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HOS-100995 · has-contraindication-information · PDF-Seite 5

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

HOS-100994 · has-indication-information · PDF-Seite 2

Breast cancer Datroway as monotherapy is indicated for the first-line treatment of adult patients with unresectable or metastatic triple-negative breast cancer (TNBC) who are not candidates for PD-1/PD-L1 inhibitor therapy (see section 5.1). Datroway as monotherapy is indicated for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-negative breast cancer who have received endocrine therapy and at least one line of chemotherapy in the advanced setting (see section 5.1).

HOS-100997 · has-interaction-information · PDF-Seite 7

No clinical drug interaction studies with datopotamab deruxtecan have been conducted. However, clinical drug-drug interaction studies were conducted with trastuzumab deruxtecan (T-DXd), which contains the same DXd payload as Datroway. The Cmax of DXd was not affected by ritonavir (inhibitor of CYP3A4 and OATP1B1 and 1B3) or itraconazole (inhibitor of CYP3A4). The AUC was increased 1.2-fold by both inhibitors which was not considered clinically relevant. Therefore, inhibitors of CYP3A4, OATP1B1 and OATP1B3 will most likely not have a clinically relevant effect on the PK of deruxtecan released from datopotamab deruxtecan.

HOS-100998 · has-pregnancy-information · PDF-Seite 7

Women of childbearing potential/Contraception in females and males The pregnancy status of women of childbearing potential should be verified prior to initiation of Datroway. Women of childbearing potential should use effective contraception during treatment with Datroway and for at least 7 months following the last dose. Men with female partners of childbearing potential should use effective contraception during treatment with Datroway and for at least 4 months following the last dose. Pregnancy There are no available data on the use of Datroway in pregnant women. However, based on findings in animals and its mechanism of action, the topoisomerase I inhibitor component, DXd, can be expected to cause embryo-foetal harm when administered to pregnant women (see section 5.3). Datroway is not recommended during pregnancy and in women of childbearing potential not using contraception. Patients should be informed of the potential risks to the foetus before they become pregnant and to contact their doctor immediately if they become pregnant. Breast-feeding It is not known if datopotamab deruxtecan is excreted in human milk. Human IgG is excreted in human milk. Because of the potential for serious adverse reactions in breast-fed children, women should discontinue breast-feeding prior to initiating treatment with Datroway. Women may begin breast-feeding 1 month after concluding treatment. Fertility No human data on the effect of datopotamab deruxtecan on fertility are available. Based on results from animal toxicity studies, Datroway may impair male and female reproductive function and fertility (see section 5.3). 7 Both men and women should seek advice on fertility preservation before treatment. It is not known whether datopotamab deruxtecan or its metabolites are found in seminal fluid. Male patients must not freeze or donate sperm throughout the treatment period, and for at least 4 months after the final dose of Datroway. Female patients must not donate, or retrieve for their own use, ova throughout the treatment period and for at least 7 months after the final dose of Datroway.

HOS-100996 · has-warning-information · PDF-Seite 5

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. Interstitial lung disease/pneumonitis Cases of interstitial lung disease (ILD), including pneumonitis, have been reported in patients treated with Datroway (see section 4.8). Fatal outcomes have been observed. Patients should be advised to immediately report cough, dyspnoea, fever, and/or any new or worsening respiratory symptoms. Patients should be monitored for signs and symptoms of ILD/pneumonitis. Evidence of ILD/pneumonitis should be promptly investigated. Patients with suspected ILD/pneumonitis should be evaluated by radiographic imaging. Consultation with a pulmonologist should be considered. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g. ≥ 0.5 mg/kg/day prednisolone or equivalent). Datroway should be delayed until recovery to Grade 0 and may be resumed according to instructions in Table 2 (see section 4.2). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g. ≥ 1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Datroway should be permanently discontinued in patients who are 5 diagnosed with symptomatic (Grade 2 or greater) ILD/pneumonitis (see section 4.2). Patients with a history of ILD/pneumonitis may be at increased risk of developing ILD/pneumonitis and should be monitored carefully. Hypersensitivity Serious, anaphylactic reactions have been observed with datopotamab deruxtecan. Patients should be observed closely for hypersensitivity/allergic reactions, which may have the same clinical presentation as an infusion-related reaction. Medicinal products to treat such reactions, as well as emergency equipment, should be available for immediate use. In the event of a serious hypersensitivity reaction, datopotamab deruxtecan treatment must be immediately and permanently discontinued. Keratitis Datroway can cause ocular surface undesirable effects including keratitis. Signs and symptoms of keratitis may include dry eye, increased lacrimation, photophobia, and detrimental changes to vision (see section 4.8). Patients should be advised to use preservative-free lubricant eye drops several times daily for prophylaxis. Patients should be advised to avoid use of co

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