TEPKINLY

4). Posology Recommended pre-medication and dose schedule Details on recommended premedication for cytokine release syndrome (CRS) are shown in Table 1. Table 1 – Epcoritamab premedication and CRS prophylaxis Cycle Patient requiring premedication Premedication Corticosteroid prophylaxis Cycle 1 All patients 30-120 minutes prior to each weekly administration of epcoritamab • Dexamethasoneb (15 mg oral or intravenous) or Prednisolone (100 mg oral or IV) or equivalent • Diphenhydramine (50 mg oral or IV) or equivalent • Paracetamol (1000 mg oral) Prednisolone (100 mg oral or IV) or equivalent for three consecutive days following each weekly administration of epcoritamab in Cycle 1 Cycle 2 and beyond Patients who experienced Grade 2 or 3a CRS with previous dose 30-120 minutes prior to next administration of epcoritamab after a grade 2 or 3a CRS event • Dexamethasoneb (15 mg oral or intravenous) or Prednisolone (100 mg oral or IV) or equivalent Prednisolone (100 mg oral or IV) or equivalent for three consecutive days following the next administration of epcoritamab until epcoritamab is given without subsequent CRS of any grade a Patients will be permanently discontinued from epcoritamab after a Grade 4 CRS event.

bDexamethasone is the preferred corticosteroid for CRS prophylaxis based on the GCT3013-01 Optimisation study. Administer Tepkinly according to the step-up dose schedule in 28-day cycles outlined in Table 2 for patients with diffuse large B-cell lymphoma and Table 3 for patients with follicular lymphoma.

Tepkinly is for subcutaneous (SC) injection only. Table 2 - Tepkinly 2-step step-up dose schedule for patients with diffuse large B- cell lymphoma Table 3 - Tepkinly 3-step step-up dose schedule for patients with follicular lymphoma Tepkinly should be administered until disease progression or unacceptable toxicity.

e. an initial transient increase in tumour size or small new lesions within the first few months followed by tumour shrinkage) have been observed. It is recommended to continue treatment for clinically stable patients with initial evidence of disease progression until disease progression is confirmed.

Tepkinly should be administered to well hydrated patients. 8 mg is an intermediate dose and 48 mg is a full dose. 8 mg is an intermediate dose, 3 mg is a second intermediate dose and 48 mg is a full dose. Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) and herpes virus infections is strongly recommended especially during concurrent use of steroids.

Summary of the safety profile The safety of epcoritamab was evaluated in a non-randomised, single-arm GCT3013- 01 study in 382 patients with relapsed or refractory large B-cell lymphoma (N=167), follicular lymphoma (N=129) and follicular lymphoma (3-step step-up dose schedule N=86) after two or more lines of systemic therapy and included all the patients who enrolled to the 48 mg dose and received at least one dose of epcoritamab.

The following adverse reactions have been reported with epcoritamab during clinical studies and post marketing experience. 9 months (range: <1 to 30 months). The most common adverse reactions (≥20%) were CRS (56%), injection site reactions (40%), fatigue (32%), viral infection (28%), neutropenia (28%), muscoskeletal pain (27%), pyrexia (22%), and diarrhoea (21%).

4%). Serious adverse reactions occurred in 50% of patients. The most common serious adverse reaction (≥10%) was CRS (34%). 3%) patient). 8% of patients. 3%) patient each. Dose delays due to adverse reactions occurred in 42% of patients. 7%).

Tabulated list of adverse reactions Adverse reactions for epcoritamab from clinical studies (Table 7) are listed by MedDRA system organ class and are based on the following convention: 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); and very rare (< 1/10 000).

0 a Viral infection includes COVID-19, cytomegalovirus chorioretinitis, cytomegalovirus colitis, cytomegalovirus infection, cytomegalovirus infection reactivation, gastroenteritis viral, herpes simplex, herpes simplex reactivation, herpes virus infection, herpes zoster, oral herpes, post- acute COVID-19 syndrome, and varicella zoster virus infection b Pneumonia includes COVID-19 pneumonia and pneumonia c Upper respiratory tract infection includes laryngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, rhinovirus infection, and upper respiratory tract infection d Fungal infection includes candida infection, oesophageal candidiasis, oral candidiasis and oropharyngeal candidiasis e Sepsis includes bacteraemia, sepsis, and septic shock f Neutropenia includes neutropenia and neutrophil count decreased g Anaemia includes anaemia and serum ferritin decreased h Thrombocytopenia includes platelet count decreased and thrombocytopenia i Lymphopenia includes lymphocyte count decreased and lymphopenia j Events graded using American Society for Transplantation and Cellular Therapy (ASTCT) consensus criteria k Clinical Tumour Lysis Syndrome was graded based on Cairo-Bishop l Cardiac arrhythmias include bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia m Abdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness n Rash includes rash, rash erythematous, rash macular, rash maculo-papular, rash popular, rash pruritic, rash pustular and rash vesicular o Musculoskeletal pain includes back pain, bone pain, flank […]

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. 8). The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia.

Other signs and symptoms of CRS include chills, tachycardia, headache and dyspnoea. Most CRS events occurred in Cycle 1 and were associated with the first full dose of epcoritamab. 2). Patients should be monitored for signs and symptoms of CRS following epcoritamab administration.

2, Table 4). Counsel patients on the signs and symptoms associated with CRS and instruct patients to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time. 2). Patients with DLBCL should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of CRS.

Haemophagocytic lymphohistiocytosis (HLH) Haemophagocytic lymphohistiocytosis (HLH), including fatal cases, have been reported in patients receiving epcoritamab. HLH is a life-threatening syndrome characterised by fever, skin rash, lymphadenopathy, hepato- and/or splenomegaly and cytopenias.

HLH should be considered when the presentation of CRS is atypical or prolonged. Patients should be monitored for clinical signs and symptoms of HLH. For suspected HLH, epcoritamab must be interrupted for diagnostic workup and treatment for HLH initiated.

If HLH is confirmed, administration of Tepkinly should be discontinued. 8). ICANS may manifest as aphasia, altered level of consciousness, impairment of cognitive skills, motor weakness, seizures, and cerebral oedema. The majority of cases of ICANS occurred within the Cycle 1 of epcoritamab treatment, however some occurred with delayed onset.

Patients should be monitored for signs and symptoms of ICANS following epcoritamab administration. 2, Table 5). Patients with DLBCL should be hospitalised for 24 hours after administration of the Cycle 1 Day 15 dose of 48 mg to monitor for signs and symptoms of ICANS.

1.