Tepkinly

Tepkinly must only be administered under the supervision of a healthcare professional qualified in the use of anti-cancer therapy. At least 1 dose of tocilizumab for use in the event of CRS should be available prior to epcoritamab administration for Cycle 1.

Access to an additional dose of tocilizumab within 8 hours of use of the previous tocilizumab dose should be available. Posology Recommended pre-medication and dose schedule Tepkinly should be administered according to the following step-up dose schedule in 28-day cycles which is outlined in Table 1 for patients with diffuse large B-cell lymphoma and Table 2 for patients with follicular lymphoma.

3 Table 1 Tepkinly 2-step step-up dose schedule for patients with diffuse large B-cell lymphoma Table 2 Tepkinly 3-step step-up dose schedule for patients with follicular lymphoma Tepkinly should be administered until disease progression or unacceptable toxicity.

Details on recommended pre-medication for cytokine release syndrome (CRS) are shown in Table 3. 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.

4 administration of epcoritamab until epcoritamab is given without subsequent any grade of CRS aPatients 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.

Prophylaxis against Pneumocystis jirovecii pneumonia (PCP) and herpes virus infections is strongly recommended especially during concurrent use of steroids. Tepkinly should be administered to adequately hydrated patients. It is strongly recommended that all patients adhere to the following fluid guidelines during Cycle 1, unless medically contraindicated: • 2-3 L of fluid intake during the 24 hours prior to each epcoritamab administration • Hold antihypertensive medications for 24 hours prior to each epcoritamab administration • Administer 500 ml isotonic intravenous (IV) fluids on the day of epcoritamab prior to dose administration; AND • 2-3 L of fluid intake during the 24 hours following each epcoritamab administration.

Patients at an increased risk for clinical tumour lysis syndrome (CTLS) are recommended to receive hydration and prophylactic treatment with a uric acid lowering agent. Patients should be monitored for signs and symptoms of CRS and/or immune effector cell-associated neurotoxicity syndrome (ICANS) and managed per current practice guidelines following epcoritamab administration.

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, injection site reactions, fatigue, viral infection, neutropenia, musculoskeletal pain, pyrexia, and diarrhoea.

Serious adverse reactions occurred in 50% of patients. The most frequent serious adverse reaction (≥ 10%) was cytokine release syndrome (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).

Within each frequency grouping, adverse reactions are presented in order of decreasing seriousness. 0 aViral 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 bPneumonia includes COVID-19 pneumonia and pneumonia cUpper respiratory tract infection includes laryngitis, pharyngitis, respiratory syncytial virus infection, rhinitis, rhinovirus infection, and upper respiratory tract infection dFungal infection includes candida infection, oesophageal candidiasis, oral candidiasis and oropharyngeal candidiasis eSepsis includes bacteraemia, sepsis, and septic shock fNeutropenia includes neutropenia and neutrophil count decreased gAnaemia includes anaemia and serum ferritin decreased hThrombocytopenia includes platelet count decreased and thrombocytopenia iLymphopenia 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 lCardiac arrhythmias include bradycardia, sinus bradycardia, sinus tachycardia, supraventricular tachycardia, and tachycardia mAbdominal pain includes abdominal discomfort, abdominal pain, abdominal pain lower, abdominal pain upper, and abdominal tenderness nRash includes rash, rash erythematous, rash macular, rash maculo-papular, rash papular, rash pruritic, rash pustular, and rash vesicular oMusculoskeletal pain includes back pain, bone pain, flank pain, musculoskeletal chest pain, musculoskeletal pain, myalgia, neck pain, non-cardiac chest pain, pain, pain in extremity, and spinal pain pInjection site reactions include […]

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. Cytokine release syndrome (CRS) CRS, which may be life-threatening or fatal, occurred in patients receiving epcoritamab.

The most common signs and symptoms of CRS include pyrexia, hypotension and hypoxia. Other signs and symptoms of CRS in more than two patients 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). Patients should be counselled on the signs and symptoms associated with CRS and patients should be instructed to contact their healthcare professional and seek immediate medical attention should signs or symptoms occur at any time.

2). 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. Immune effector cell-associated neurotoxicity syndrome (ICANS) ICANS, including fatal events, have occurred in patients receiving epcoritamab. 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 Cycle 1 of epcoritamab treatment, however some occurred with delayed onset. 11 Patients should be monitored for signs and symptoms of ICANS following epcoritamab administration. 2, Table 5).

1.