Zynlonta

Zynlonta must only be administered under the supervision of a healthcare professional experienced in the diagnosis and treatment of cancer patients. 075 mg/kg every 21 days for subsequent cycles until disease progression or unacceptable toxicity.

Premedication with dexamethasone Unless contraindicated, dexamethasone 4 mg is to be administered orally or intravenously twice daily for 3 days, beginning the day before administering Zynlonta to mitigate pyrrolobenzodiazepine (PBD)-related toxicities.

If dexamethasone administration does not begin the day before Zynlonta, oral or intravenous dexamethasone should begin at least 2 hours prior to administration of Zynlonta. 3 Delayed or missed doses If a planned dose of Zynlonta is missed, it should be administered as soon as possible, and the schedule of administration should be adjusted to maintain a 21-day interval between doses.

8), see Table 1 below. 8) Grade 3 or higher Withhold Zynlonta until the toxicity resolves to Grade 1 or less If dosing is delayed by more than 3 weeks due to toxicity related to Zynlonta, subsequent doses should be reduced by 50%. 075 mg/kg for Cycle 3.

If toxicity reoccurs after two dose reductions following an adverse reaction, permanent discontinuation of Zynlonta should be considered. 1). 2). Zynlonta has not been studied in patients with severe renal impairment (CLcr 15 to 29 ml/min).

The effect of severe renal impairment, and end-stage renal disease, with or without haemodialysis, on loncastuximab tesirine pharmacokinetics is unknown. Additional monitoring for adverse reactions may be warranted in these patients when loncastuximab tesirine is administered.

For SG3199, data collected in an animal model (rat) show minimal renal excretion. No clinical data are available. 5 × ULN and any AST). 5 × ULN and any AST). In patients with hepatic impairment, monitoring for adverse reactions is recommended.

Paediatric population The safety and efficacy of loncastuximab tesirine in children and adolescents aged less than 18 years have not yet been established. No data are available. 4 Method of administration Zynlonta is for intravenous use.

The infusion is administered over 30 minutes through an intravenous line. 8). The infusion site should be monitored for possible subcutaneous infiltration during medicinal product administration. Zynlonta must be reconstituted and diluted using aseptic technique under the supervision of a healthcare professional.

8%). 9% each). 5%). 4% each). 4%. 9%). 15 mg/kg) in two monotherapy studies, of whom 145 patients participated in the Phase 2 pivotal study ADCT-402-201 (LOTIS-2) and 70 patients participated in the Phase 1 study (ADCT-402-101). These patients were exposed to Zynlonta during a median of 45 days (range 1 to 569 days).

Unless otherwise stated, the frequencies of adverse reactions are based on all-cause adverse event frequencies in the clinical studies, where a proportion of the events for an adverse reaction may have other causes than the medicinal product, such as the disease, other medicinal products or unrelated causes.

Adverse reactions are presented according to the MedDRA system organ class (SOC) and classified, by frequency, as 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), not known (cannot be estimated from the available data).

Within each frequency grouping, adverse reactions are presented by seriousness from highest to lowest.

Table 2:

Adverse reactions reported for Zynlonta in adult patients with relapsed or refractory DLBCL MedDRA SOC Very common Common Uncommon Infections and infestations Pneumoniaa (includes lung infection) Upper respiratory tract infection Sepsis Lower respiratory tract infection Blood and lymphatic system disorders Anaemia Neutropenia Thrombocytopenia Febrile neutropenia Metabolism and nutrition disorders Decreased appetite Fluid retention Fluid overload Nervous system disorders Lethargy Cardiac disorders Pericardial effusion Pericarditis Respiratory, thoracic and mediastinal disorders Pleural effusion Dyspnoeab Gastrointestinal disorders Abdominal painc Diarrhoea Nausea Vomiting Constipation Ascites 8 Skin and subcutaneous tissue disorders Rash Pruritus Erythema Photosensitivity reaction Maculopapular rash Skin hyperpigmentation Pruritic rash Swelling face Bullous dermatitis Pustular rash Musculoskeletal and connective tissue disorders Neck pain Pain in extremity Back pain Musculoskeletal pain Myalgia Musculoskeletal chest pain Musculoskeletal discomfort Limb discomfort General disorders and administration site conditions Oedema peripheral Fatigue Face oedema Asthenia Peripheral swelling Swelling Non-cardiac chest pain Generalised oedema Oedema Investigations γ-glutamyltransferase increased Aspartate aminotransferase increased Alanine aminotransferase increased Blood alkaline phosphatase increased a Grade 5 associated adverse reactions b Dyspnoea includes dyspnoea, and dyspnoea exertional c Abdominal pain includes abdominal pain, abdominal discomfort, abdominal pain lower, and abdominal pain upper Description of selected adverse reactions Effusion and oedema Serious effusion and oedema occurred in patients treated with Zynlonta.

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). Patients should be monitored for new or worsening oedema or effusions.

Zynlonta should be withheld for Grade 2 or greater oedema or effusion until the toxicity resolves. Diagnostic imaging should be considered in patients who develop symptoms of pleural effusion or pericardial effusion, such as new or worsened dyspnoea, chest pain, and/or ascites such as swelling in the abdomen and bloating.

2). 8). Complete blood cell counts should be monitored prior to each dose of Zynlonta. Cytopenia may require more frequent lab monitoring and/or interruption, dose reduction, or discontinuation of Zynlonta. 2). 8). Patients should be monitored for any new or worsening signs or symptoms consistent with infection.

2). Photosensitivity and cutaneous reactions Serious cutaneous reactions have been reported in patients treated with Zynlonta. 8). Patients should be monitored for new or worsening cutaneous reactions, including photosensitivity reactions.

2). Patients should be advised to minimise or avoid exposure to direct natural or artificial sunlight including exposure through glass windows. Patients should be instructed to protect skin from exposure to sunlight by wearing sun-protective clothing and/or the use of sunscreen products.

3). Embryo-foetal toxicity Zynlonta may cause embryo-foetal harm when administered to a pregnant woman because it contains a genotoxic compound (SG3199), which affects actively dividing cells. Pregnant women should be advised of the potential risk to the foetus.

Women of childbearing potential should be advised to use effective contraception during treatment with Zynlonta and for 10 months after the last dose. 6). 3).

1.