Aucatzyl · 4.8 Undesirable effects · 1

HOS-288739 · has-adverse-reaction-information · PDF-Seite 15

Summary of the safety profile The most common non-laboratory adverse reactions of any grade included CRS (68.5%), infections - pathogen unspecified (44.9%), musculoskeletal pain (31.5%), pyrexia (29.1%), pain (27.6%), nausea (26.0%), diarrhoea (25.2%), headache (23.6%), fatigue (22.0%), and haemorrhage (21.3%). The most common non-laboratory grade 3 or higher adverse reactions were infections - pathogen unspecified (24.4%), febrile neutropenia (23.6%), viral infections (13.4%), and bacterial infectious disorders (11.0%). The most common serious adverse reactions of any grade included infections - pathogen unspecified (20.5%), febrile neutropenia (13.4%), ICANS (9.4%), CRS (7.9%), sepsis (7.9%) and pyrexia (7.1%). The most common grade 3 or 4 laboratory abnormalities included neutropenia (98.4%), leucocytes decreased (97.6%), lymphocytes decreased (95.3%), thrombocytopenia (77.2%), and anaemia (65.4%). The lymphodepleting chemotherapy prior to Aucatzyl administration also contributes to the laboratory abnormalities. Tabulated list of adverse reactions Table 4 summarises the adverse reactions in a total of 127 patients exposed to Aucatzyl in the Phase Ib and Phase II FELIX study. These reactions are presented by Medical Dictionary for Regulatory Activities system organ class and by frequency. Frequencies are defined as: very common (≥ 1/10), and common (≥ 1/100 to < 1/10). Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 15 Table 4: Adverse drug reactions identified with Aucatzyl System organ Frequency Adverse reaction class (SOC) Infections and infestations Very common Infections – pathogen unspecified Bacterial infectious disorders COVID-19 Viral infectious disorders excluding COVID-19 Fungal infectious disorders Sepsis Blood and lymphatic system disorders Very common Neutropeniaa Leukopeniaa Lymphopeniaa Thrombocytopeniaa Anaemiaa

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HOS-288735 · has-contraindication-information · PDF-Seite 7

Hypersensitivity to the active substance or to any of the excipients listed in section 6.1. Contraindications of the lymphodepleting chemotherapy must be considered.

HOS-288734 · has-indication-information · PDF-Seite 2

Aucatzyl is indicated for the treatment of adult patients 26 years of age and above with relapsed or refractory (r/r) B cell precursor acute lymphoblastic leukaemia (B ALL). 2

HOS-288737 · has-interaction-information · PDF-Seite 14

No interaction studies have been performed. Prophylactic use of systemic corticosteroids may interfere with the activity of Aucatzyl. Prophylactic use of systemic corticosteroids is therefore not recommended before infusion (see section 4.2). Administration of tocilizumab or corticosteroids for the treatment of CRS and ICANS did not affect the rate or extent of expansion and persistency. Live vaccines The safety of immunisation with live viral vaccines during or following treatment with Aucatzyl has not been studied. As a precautionary measure, vaccination with live vaccines is not recommended for at least 6 weeks prior to the start of lymphodepletion chemotherapy, during Aucatzyl treatment, and until immune recovery following treatment.

HOS-288738 · has-pregnancy-information · PDF-Seite 14

Women of childbearing potential / Contraception in males and females The pregnancy status of women of childbearing potential must be verified before starting Aucatzyl treatment. Aucatzyl is not recommended for women of childbearing potential who are not using contraception. See the prescribing information for lymphodepleting therapy for information on the need for effective contraception in patients who receive the lymphodepleting chemotherapy. There is insufficient exposure data to provide a recommendation concerning duration of contraception following treatment with Aucatzyl. Pregnancy There is a limited amount of data from the use of obecabtagene autoleucel in pregnant women. No animal reproductive and developmental toxicity studies have been conducted with Aucatzyl to assess whether it can cause foetal harm when administered to a pregnant woman (see section 5.3). It is not known if obecabtagene autoleucel has the potential to be transferred to the foetus. Based on the mechanism of action, if the transduced cells cross the placenta, they may cause foetal toxicity, including B cell lymphocytopenia. Therefore, Aucatzyl is not recommended for women who are pregnant. Pregnant women must be advised on the potential risks to the foetus. 14 Pregnancy after Aucatzyl therapy must be discussed with the treating physician. Assessment of immunoglobulin levels and B cells in newborn infants of mothers treated with Aucatzyl must be considered. Breast-feeding It is unknown whether obecabtagene autoleucel cells are excreted in human milk or transferred to the breast-feeding child. A risk to the breast-fed infant cannot be excluded. Breast-feeding women must be advised by the treating physician of the potential risk to the breast-fed child. Fertility There are no clinical data on the effect of Aucatzyl on fertility. Effects on male and female fertility have not been evaluated in animal studies.

HOS-288736 · has-warning-information · PDF-Seite 7

Traceability The traceability requirements of cell-based advanced therapy medicinal products must apply. To ensure traceability the name of the product, the batch number and the name of the treated patient must be kept for a period of 30 years after the expiry date of the product. Autologous use Aucatzyl is intended solely for autologous use and must not, under any circumstances, be administered to other patients. Aucatzyl must not be administered if the information on the product labels and RfIC do not match the patient’s identity. 7 General The availability of Aucatzyl must be confirmed before starting the lymphodepleting chemotherapy regimen. Patients should be clinically re-assessed prior to administration of lymphodepleting chemotherapy and Aucatzyl to ensure that there are no reasons to delay therapy. Warnings and precautions of lymphodepleting chemotherapy must be considered. Reasons to delay or discontinue treatment Aucatzyl should not be administered to patients with clinically significant active systemic infections, in the presence of significant safety concerns following lymphodepleting chemotherapy or patients who require supplementary oxygen for treatment of their medical condition (refer to section 4.2). Cytokine release syndrome (CRS) CRS was reported following treatment with Aucatzyl (see section 4.8). CRS is more probable in patients with a high tumour burden. CRS may appear up to 23 days post-infusion. Severe adverse reactions have been reported after Aucatzyl infusion. In general, CRS following CAR T treatment can be life-threatening. Patients should be counselled to seek immediate medical attention should signs or symptoms of CRS occur at any time. At the first sign of CRS, the patient should be timely evaluated for hospitalisation and for management as per guidance in Table 2 and for administration of supportive care. Use of myeloid growth factors such as granulocyte colony-stimulating factor (G-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF) should be avoided during CRS, given the potential to worsen CRS symptoms. Patients should be monitored daily for 14 days after the first infusion for signs and symptoms of potential CRS. The most common manifestations of CRS included fever, hypotension, and hypoxia. Frequency of monitoring after the first 14 days should be carried out at the physician’s discretion and should be continued for at least 4 weeks a

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