Hetronifly · 4.4 Special warnings and precautions for use · 1

HOS-100648 · has-adverse-reaction-information · PDF-Seite 10

Summary of the safety profile The safety of serplulimab in combination with chemotherapy is based on pooled data in 1 343 patients. The most common adverse reactions were anaemia (80.2%), neutropenia (74.5%), leukopenia (71.6%), thrombocytopenia (53.8%), nausea (44.4%), decreased appetite (36.0%), alopecia (33.6%), hypoproteinaemia (31.3%), asthenia (29.9%), and vomiting (28.2%). The most common Grade ≥ 3 adverse reactions were neutropenia (46.2%), leukopenia (27.3%), anaemia (25.8%), thrombocytopenia (15.3%), hyponatraemia (6.9%), and pneumonia (5.6%). The most common serious adverse reactions were thrombocytopenia (8.4%), pneumonia (6.6%), neutropenia (6.0%), leukopenia (5.9%), anaemia (4.5%), and pneumonitis (3.3%). The most common immune-mediated adverse reactions were hypothyroidism (11.5%), immune- mediated skin reactions (7.6%), hyperthyroidism (7.1%), immune-mediated lung disease (5.5%), abnormal liver function (3.2%), immune-mediated nephritis and renal insufficiency (3.1%), and immune-mediated colitis (1.6%). Serplulimab was discontinued due to adverse reactions in 8.1% of patients. The most common adverse reactions leading to treatment discontinuation were pneumonitis (1.6%) and pneumonia (1.3%). 10 Tabulated list of adverse reactions Adverse reactions reported in clinical trial and in post-marketing experience are listed by system organ class and frequency (see Table 2). Unless otherwise stated, the frequencies of adverse reactions are based on all-cause adverse event frequencies identified in trials in which 1343 patients were exposed to serplulimab in combination with chemotherapy. See section 5.1 for information about the main characteristics of patients in the pivotal clinical trials. 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 the available data). Within each frequency grouping, adverse reactions are presented in the order of decreasing seriousness. Table 2. Adverse reactions in patients treated with serplulimab* Serplulimab in combination with chemotherapy Infections and infestations Very common pneumonia a Common urinary tract infection b, respiratory tract infection c, skin infection Uncommon septic shock Rare gastr

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HOS-100644 · has-contraindication-information · PDF-Seite 6

Hypersensitivity to active substance or to any of the excipients listed in section 6.1.

HOS-100643 · has-indication-information · PDF-Seite 2

Small cell lung cancer (SCLC) HETRONIFLY in combination with carboplatin and etoposide is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). Non-small cell lung carcinoma (NSCLC) HETRONIFLY in combination with carboplatin and pemetrexed is indicated for the first-line treatment of adult non-squamous NSCLC patients with no EGFR, ALK or ROS1 positive mutations and who have:  locally advanced NSCLC who are not candidates for surgery or radiotherapy, or  metastatic NSCLC. HETRONIFLY in combination with carboplatin and nab-paclitaxel is indicated for the first-line treatment of adult patients with unresectable, locally advanced or metastatic squamous non-small cell lung carcinoma. Oesophageal squamous cell carcinoma (OSCC) 2 HETRONIFLY in combination with fluoropyrimidine- and platinum-based chemotherapy is indicated for the first-line treatment of adult patients with unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma whose tumours express PD-L1 with a CPS ≥ 5.

HOS-100646 · has-interaction-information · PDF-Seite 9

Drug-drug interaction studies have not been conducted. As monoclonal antibodies are not metabolised by cytochrome P450 (CYP) enzymes or other drug metabolising enzymes, inhibition, or induction of these enzymes by co-administered medicinal products is not anticipated to affect the pharmacokinetics of HETRONIFLY. The use of systemic corticosteroids or immunosuppressants before starting serplulimab should be avoided because of their potential interference with the pharmacodynamic activity and efficacy. However, systemic corticosteroids or other immunosuppressants can be used to treat immune- mediated adverse reactions after starting serplulimab (see section 4.4). 9

HOS-100647 · has-pregnancy-information · PDF-Seite 10

Women of childbearing potential/contraception Women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last dose of serplulimab. Pregnancy There is no data on the use of serplulimab in pregnant women. Animal studies have demonstrated that inhibition of the PD-1 pathway causes embryofoetal toxicity (see section 5.3). Human IgG is known to cross the placental barrier and serplulimab is an IgG4; therefore, it has the potential to be transmitted from the mother to the developing foetus. Serplulimab is not recommended during pregnancy and in women of childbearing potential not using contraception. Breast-feeding It is unknown whether serplulimab is excreted in human milk. Human IgGs are known to be excreted in breast milk during the first few days after birth, which is decreasing to low concentrations soon; consequently, a risk to the breast-fed infant cannot be excluded during this short period. Afterwards, serplulimab could be used during breast-feeding if clinically needed. Fertility Studies to evaluate fertility have not been performed. Thus, the effect of serplulimab on male and female fertility is unknown.

HOS-100645 · has-warning-information · PDF-Seite 6

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. Assessment of PD-L1 status When assessing the PD-L1 status of the tumour, it is important that a well validated methodology is chosen to minimise false negative or false positive determinations. Immune-mediated adverse reactions Immune-mediated adverse reactions, including severe and fatal cases, have occurred in patients receiving serplulimab (see section 4.8). Most immune-mediated adverse reactions occurring during treatment were reversible and managed by withholding treatment, administration of corticosteroids, and/or supportive care (see section 4.2). Immune-mediated adverse reactions have also occurred up to 3.6 months after the last dose. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. For suspected immune-mediated adverse reactions, adequate evaluation to confirm aetiology or exclude other causes should be ensured. Based on the severity of the adverse reaction, treatment should be withheld, and corticosteroid administered. For most Grade 2 and some specific Grade 3 or 4 immune-mediated adverse reactions, administration should be withheld until recover or improve to Grade 1. Serplulimab must be permanently discontinued for any Grade 4 and some specific Grade 3 immune-mediated adverse reactions. For Grade 3, 4 and some specific Grade 2 immune-mediated adverse reactions (e.g., immune-mediated pneumonitis, immune-mediated myocarditis), corticosteroid (1-2 mg/kg/day prednisone or equivalent) and other symptomatic treatments should be given according to the clinical symptoms until recover or improve to Grade 1. Upon improvement to Grade ≤ 1, corticosteroid taper should be initiated and continued over at least 1 month. Rapid tapering may lead to worsening or recurrence of the adverse reaction. Non-corticosteroid immunosuppressive therapy (e.g., infliximab) should be added if there is worsening or no improvement despite corticosteroid use. Immune-mediated lung disease Immune-mediated pneumonitis, including fatal cases, has been reported in patients receiving HETRONIFLY (see section 4.8). Patients should be monitored for signs and symptoms of immune-mediated pneumonitis such as radiographic changes (e.g., focal ground glass opacities, patchy filtrates), dyspnoea, and hypoxia. Suspected immune-mediated pneumonitis should be confirmed wit

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