Jemperli · 4.4 Special warnings and precautions for use · 1

HOS-099343 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile Dostarlimab is most commonly associated with immune-related adverse reactions. Most of these, including severe reactions, resolved following initiation of appropriate medical therapy or withdrawal of dostarlimab (see “Description of selected adverse reactions” below). Dostarlimab in monotherapy The safety of dostarlimab has been evaluated in 605 patients with EC or other advanced solid tumours who received dostarlimab monotherapy in the GARNET study, including 153 patients with advanced or recurrent dMMR/MSI-H EC. Patients received doses of 500 mg every 3 weeks for 4 cycles followed by 1000 mg every 6 weeks for all cycles thereafter. In patients with advanced or recurrent solid tumours (N = 605), the most common adverse reactions (> 10 %) were anaemia (28.6 %), diarrhoea (26.0 %), nausea (25.8 %), vomiting (19.0 %), arthralgia (17.0 %), pruritus (14.2 %), rash (13.2 %), pyrexia (12.4 %), aspartate aminotransferase increased (11.2 %) and hypothyroidism (11.2 %). JEMPERLI was permanently discontinued due to adverse reactions in 38 (6.3 %) patients; most of them were immune-related events. Adverse reactions were serious in 11.2 % of patients; most serious adverse reactions were immune-related adverse reactions (see section 4.4). 10 The safety profile for patients with dMMR/MSI-H EC in the GARNET study (N = 153) was not different from that of the overall monotherapy population presented in Table 4. Dostarlimab in combination with carboplatin and paclitaxel The safety of dostarlimab has been evaluated in 241 patients with primary advanced or recurrent EC who received dostarlimab in combination with carboplatin and paclitaxel in the RUBY study. Patients received doses of 500 mg dostarlimab every 3 weeks for 6 cycles followed by 1000 mg every 6 weeks for all cycles thereafter. In patients with primary advanced or recurrent EC (N = 241), the most common adverse reactions (≥ 10 %) were rash (23.2 %), rash maculopapular (14.5 %), hypothyroidism (14.5 %), pyrexia (12.9 %), alanine aminotransferase increased (12.9 %), aspartate aminotransferase increased (12.0 %) and dry skin (10.0 %). JEMPERLI was permanently discontinued due to adverse reactions in 12 (5.0 %) patients; most were immune-related events. Adverse reactions were serious in 5.8 % of patients. The most frequent (>1 %) serious adverse reaction was pyrexia (2.9 %). The most frequent (>10 %) immune-related adverse

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HOS-099339 · has-contraindication-information · PDF-Seite 6

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

HOS-099338 · has-indication-information · PDF-Seite 2

JEMPERLI is indicated in combination with carboplatin and paclitaxel for the first-line treatment of adult patients with primary advanced or recurrent endometrial cancer (EC) and who are candidates for systemic therapy. JEMPERLI is indicated as monotherapy for the treatment of adult patients with mismatch repair deficient (dMMR)/ microsatellite instability-high (MSI-H) recurrent or advanced EC that has progressed on or following prior treatment with a platinum-containing regimen.

HOS-099341 · has-interaction-information · PDF-Seite 9

No interaction studies have been performed. Monoclonal antibodies (mAb) such as dostarlimab are not substrates for cytochrome P450 or active substance transporters. Dostarlimab is not a cytokine and is unlikely to be a cytokine modulator. Additionally, pharmacokinetic interaction of dostarlimab with small molecule active substances is not expected. There is no evidence of interaction mediated by non-specific clearance of lysosome degradation for antibodies.

HOS-099342 · has-pregnancy-information · PDF-Seite 9

Women of childbearing potential/Contraception There is a risk associated with the administration of dostarlimab to women of childbearing potential. Women of childbearing potential must use effective contraception during treatment with dostarlimab and until 4 months after the last dose of dostarlimab. 9 Pregnancy There are no or limited amount of data on the use of dostarlimab in pregnant women. Based on its mechanism of action, dostarlimab can cause foetal harmful pharmacological effects when administered during pregnancy. Animal reproduction and development studies have not been conducted with dostarlimab; however, inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing foetus resulting in foetal death (see section 5.3). Human immunoglobulins (IgG4) are known to cross the placental barrier, and therefore, being an IgG4, dostarlimab has the potential to be transmitted from the mother to the developing foetus. JEMPERLI is not recommended during pregnancy and in women of childbearing potential not using effective contraception. Breast-feeding It is unknown whether dostarlimab/metabolites are excreted in human milk. A risk to the newborns/infants cannot be excluded. JEMPERLI should not be used during breast-feeding and breast-feeding should be avoided for at least 4 months after the last dose of dostarlimab. Fertility Fertility studies have not been conducted with dostarlimab (see section 5.3).

HOS-099340 · has-warning-information · PDF-Seite 6

Traceability In order to improve the traceability of biological medicinal products, the tradename and the batch number of the administered product should be clearly recorded. 6 Immune-related adverse reactions Immune-related adverse reactions, which may be severe or fatal, can occur in patients treated with antibodies blocking the programmed cell death protein-1 / programmed death-ligand 1 (PD-1/PD-L1) pathway, including dostarlimab. While immune-related adverse reactions usually occur during treatment with PD-1/PD-L1 blocking antibodies, symptoms can also manifest after discontinuation of treatment. Immune-related adverse reactions may occur in any organ or tissue and may affect more than one body system simultaneously. Important immune-related adverse reactions listed in this section are not inclusive of all possible severe and fatal immune-related reactions. Early identification and management of immune-related adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Patients should be monitored for symptoms and signs of immune-related adverse reactions. Haematological and clinical chemistries, including liver, kidney and thyroid function tests, should be evaluated at baseline and periodically during treatment. For suspected immune-related adverse reactions, adequate evaluation including specialty consultation should be ensured. Based on the severity of the adverse reaction, treatment with dostarlimab should be withheld or permanently discontinued and corticosteroids (1 to 2 mg/kg/day prednisone or equivalent) or other appropriate therapy administered (see below and section 4.2). Upon improvement to grade ≤1, corticosteroid taper should be initiated and continued for 1 month or longer. Based on limited data from clinical studies in patients whose immune-related adverse reactions could not be controlled with corticosteroid use, administration of other systemic immunosuppressants can be considered. Hormone replacement therapy for endocrinopathies should be instituted as warranted. Treatment with dostarlimab should be permanently discontinued for any grade 3 immune-related adverse reaction that recurs and for any grade 4 immune-related adverse reaction toxicity, except for endocrinopathies that are controlled with replacement hormones and unless otherwise specified in Table 3. Immune-related pneumonitis Pneumonitis has been reported in patients receiving dostarlim

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