Zepzelca

ZEPZELCA therapy should be initiated and supervised by health professionals experienced in the use of anticancer products. 2 mg/m2 every 21 days until disease progression or unacceptable toxicity when it is administered in combination with atezolizumab.

1). For the recommended intravenous or subcutaneous dose of atezolizumab, as well as for recommendations regarding dose modification due to toxicity, refer to their prescribing information. 5 x 109/L and platelet count is at least 100 x 109/L.

, cycle 2 or subsequent) will be administered every 21 days if the patient fulfils all the treatment continuation criteria listed above (see also Table 2 for dose modifications criteria for ZEPZELCA adverse reactions). If a patient does not meet the requirements for treatment continuation on Day 1 of any cycle after Cycle 1, treatment will be withheld until appropriate recovery, for a maximum of 21 days after the treatment due date.

If there is no recovery after a 21-days delay, treatment must be stopped. In case atezolizumab is discontinued due to an immune-related severe adverse reaction, treatment with lurbinectedin may be continued at its current dose as a single agent.

If immune toxicity re-occurs despite discontinuation of atezolizumab, treatment with lurbinectedin should also be discontinued. Pre-infusion medicinal products The following pre-infusion medicinal products should be administered for antiemetic prophylaxis: • Corticosteroids (intravenous dexamethasone 8 mg or equivalent) • Serotonin antagonists (intravenous ondansetron 8 mg or equivalent) Post-infusion medicinal products Primary prophylaxis with granulocyte colony-stimulating factor (G-CSF) is recommended to reduce the risk of severe neutropenia/febrile neutropenia.

If needed, post-medication can include administration of extended antiemetic treatment for 2 days: • Corticosteroids (oral dexamethasone 4 mg or equivalent), or • Serotonin antagonists (oral ondansetron 8 mg or equivalent) or • Metoclopramide (intravenous or oral 10 mg or equivalent every 8 hours) Dose adjustment for adverse reactions The recommended dose reductions for adverse reactions are listed in Table 1.

6 mg/m2) used in cases of moderated hepatic impairment or co-administration with strong or moderate CYP3A inhibitors. The recommended dose modifications for adverse reactions are presented in Table 2. 4) and other adverse reactions Grade 2 • Withhold ZEPZELCA until Grade ≤ 1 (for AST and ALT until ≤ 3 ULN), AND • Resume ZEPZELCA at same dose Grade ≥ 3 • Withhold ZEPZELCA until Grade ≤ 1 (for AST and ALT until ≤ 3 ULN).

2%). 0%). 3% of patients receiving ZEPZELCA with atezolizumab. 1%). Fatal adverse reactions occurred in 5% of patients receiving ZEPZELCA with atezolizumab, in most cases due to pneumonia and other lung infections. 8% of patients who were receiving ZEPZELCA in combination with atezolizumab.

7%). 3%). 1% of patients. 1%). * For Preferred Terms merged see footnote in Table 3. Tabulated list of adverse reactions Adverse reactions reported in IMforte clinical study are listed by MedDRA System Organ Class and by frequency in Table 3.

1 for information on the main characteristics of participants in this clinical study). Additional adverse reactions were reported post- marketing. Frequencies are defined 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); very rare (< 1/10 000); “not known (cannot be estimated from available data)”.

Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 3. 3 0 a including, Urinary tract infection, Cystitis b including Skin infection, Cellulitis c frequency not known (cannot be estimated from available data), reported in port-marketing setting (information related to grade not available).

d including Hypoesthesia, Neuropathy peripheral, Paraesthesia, Peripheral sensory neuropathy. e including Abdominal discomfort, Abdominal distension, Abdominal pain, Abdominal pain upper. f including Back pain, Musculoskeletal chest pain, Musculoskeletal pain, Myalgia, Neck pain, Pain in extremity g including Asthenia, Fatigue.

4% sepsis. The median time to first onset of neutropenia* (all grade) was 10 (range: 7-29) days. The median duration was 11 (range: 1-196) days. 4% of patients, respectively. 7% of patients. 5% ≥Grade 3), […]

Myelosupression 6 ZEPZELCA can cause severe and life-threatening myelosuppression including febrile neutropenia and sepsis. 5 x 109/L and platelet counts of less than 100 x 109/L. Full blood counts including differential white blood cells and platelet count should be monitored at baseline and prior to each cycle.

2). In case of neutrophil counts of less than 500/mm3 or any value less than lower limit of normal that is associated with infection/sepsis, the use of G-CSF is recommended. 8). Liver tests, including ALT, AST and bilirubin should be monitored prior to initiating ZEPZELCA and periodically during treatment as clinically indicated.

2). 8). The use of a central venous catheter should be considered to reduce the risk of extravasation, particularly in patients with limited venous access. Patients should be monitored for signs and symptoms of extravasation during the ZEPZELCA infusion.

If extravasation occurs, the infusion should be immediately discontinued, the infusion catheter should be removed, and the patient should be monitored for signs and symptoms of tissue necrosis. The time to onset of necrosis after extravasation may vary.

Supportive care should be administered and an appropriate medical specialist should be consulted as needed for management of signs and symptoms of extravasation. Subsequent infusions should be administered at a site that was not affected by extravasation.

8). Creatine phosphokinase (CPK) should be monitored prior to initiating ZEPZELCA and periodically during treatment as clinically indicated. If rhabdomyolysis occurs, supportive measures such as parenteral hydration, urine alkalinisation and dialysis should be promptly established, as indicated.

2]. , statins), are administered concomitantly with lurbinectedin, since the risk of rhabdomyolysis may be increased. Tumour lysis syndrome (TLS) Tumour lysis syndrome (TLS), which may be fatal, has been reported with ZEPZELCA therapy.

1. 6).