Source: European Medicines Agency (EU) Revision Year: 2025 Publisher: Henlius Europe GmbH, Sternstraße 67, 40479 Düsseldorf, Germany
Hypersensitivity to active substance or to any of the excipients listed in section 6.1.
In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Immune-related adverse reactions, including severe and fatal cases, have occurred in patients receiving serplulimab (see section 4.8). Most immune-related adverse reactions occurring during treatment were reversible and managed by withholding treatment, administration of corticosteroids, and/or supportive care (see section 4.2). Immune-related adverse reactions have also occurred up to 3.6 months after the last dose. Immune-related adverse reactions affecting more than one body system can occur simultaneously.
For suspected immune-related 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-related 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-related adverse reactions. For Grade 3, 4 and some specific Grade 2 immune-related adverse reactions (e.g., immune-related pneumonitis, immune-related 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-related 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-related pneumonitis such as radiographic changes (e.g., focal ground glass opacities, patchy filtrates), dyspnoea, and hypoxia. Suspected immune-related pneumonitis should be confirmed with radiographic imaging, and other causes excluded. For treatment modification, see section 4.2.
Immune-related colitis, including fatal cases, has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for signs and symptoms of immune-related colitis, such as abdominal pain, diarrhoea, mucus, or blood in stool. Infection and other disease-related aetiologies should be ruled out. For treatment modification, see section 4.2. The potential risk of gastrointestinal perforation should be taken into consideration and confirmed by radiographic imaging and/or endoscopy if necessary.
Immune-related hepatitis, including fatal cases, has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for changes in liver function and clinical signs and symptoms of immune-related hepatitis such as transaminase and total bilirubin elevations periodically (every month). Infection and diseases-related aetiologies should be ruled out. The frequency of liver function test should be increased, if immune-related hepatitis occurs. For treatment modification, see section 4.2.
Immune-related nephritis and renal dysfunction has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for changes in renal function and clinical signs and symptoms of immune-related nephritis and renal dysfunction periodically (every month). The frequency of renal function test should be increased, if immune-related nephritis occurs. Most patients present with asymptomatic increases in serum creatinine. Disease-related aetiologies should be ruled out. For treatment modification, see section 4.2.
Thyroid diseases:
Thyroid disorders, including hyperthyroidism, hypothyroidism, and thyroiditis, have been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for changes in thyroid function and clinical signs and symptoms of thyroid disorders. For Grade 2 or 3 symptomatic hypothyroidism, serplulimab should be withheld and thyroid hormone replacement should be initiated as needed. For Grade 2 or 3 symptomatic hyperthyroidism, serplulimab should be withheld and anti-thyroid medicinal product should be initiated as needed. If acute inflammation of the thyroid is suspected, serplulimab should be withheld and initiate hormone therapy. Treatment may be resumed when symptoms of hypothyroidism or hyperthyroidism are controlled, and thyroid function is improved. For life-threatening hyperthyroidism or hypothyroidism, serplulimab must be permanently discontinued. Thyroid function should be monitored continuously to ensure appropriate hormone replacement (see section 4.2).
Pituitary disorders:
Hypophysitis has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for signs and symptoms of hypophysitis, and other causes should be ruled out. For Grade 2 or 3 symptomatic hypophysitis, serplulimab should be withheld, and hormone replacement should be initiated as needed. If acute hypophysitis is suspected, corticosteroids should be initiated. For life-threatening Grade 4 hypophysitis, serplulimab must be permanently discontinued (see section 4.2).
Adrenal insufficiency:
Adrenal insufficiency has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for signs and symptoms, and other causes should be ruled out. For Grade 2 adrenal insufficiency, serplulimab should be withheld and hormone replacement should be initiated as needed. For life-threatening Grade 3 or 4 adrenal insufficiency, serplulimab must be permanently discontinued. Adrenal gland function and hormone levels should be monitored continuously to ensure appropriate hormone replacement (see section 4.2).
Hyperglycaemia:
Hyperglycaemia or type 1 diabetes mellitus has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for blood glucose level and related clinical signs and symptoms. Insulin replacement therapy should be initiated as needed. For type 1 diabetes mellitus with poor blood glucose control, serplulimab should be withheld, and insulin replacement therapy should be initiated until the symptoms are improved. For life-threatening Grade 4 type 1 diabetes, serplulimab must be permanently discontinued. Blood glucose levels should be monitored continuously to ensure appropriate insulin replacement (see section 4.2).
Immune-related skin adverse reactions have been reported in patients receiving serplulimab (see section 4.8). For Grade 1 or 2 rash, serplulimab can be continued, and symptomatic treatment or local corticosteroids treatment can be given. For Grade 3 rash, serplulimab should be withheld, and symptomatic treatment or local corticosteroids treatment should be given. For Grade 4 rash, Stevens-Johnson syndrome (SJS), or toxic epidermal necrolysis (TEN), serplulimab should be permanently discontinued (see section 4.2).
Immune-related pancreatitis, including increases in serum amylase and lipase levels and fatal cases, has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for changes in serum lipase and amylase (at the beginning of treatment, periodically during treatment, and as indicated based on clinical evaluation), and clinical signs and symptoms of pancreatitis. Serplulimab should be withheld for Grade 3 or 4 increase in serum amylase or lipase levels, and Grade 2 or 3 pancreatitis. For Grade 4 pancreatitis or recurrent pancreatitis of any grade, serplulimab should be permanently discontinued (see section 4.2).
Immune-related myocarditis, including fatal cases, has been reported in patients receiving serplulimab (see section 4.8). Patients should be monitored for clinical signs and symptoms of myocarditis. Suspected immune-mediated myocarditis should be confirmed with myocardial enzyme examinations, and other causes excluded. For Grade 2 myocarditis, serplulimab should be withheld, and corticosteroid treatment should be given. The safety of restarting serplulimab treatment in patients previously experiencing immune-related myocarditis is unclear. A multidisciplinary discussion is recommended before restarting serplulimab in patients with previous Grade 2 myocarditis, and the decision should be based on various clinical factors, including the degree of cardiac recovery, oncological response to the treatment, availability of alternative oncology treatments and prognosis. For Grade 3 or 4 myocarditis, serplulimab must be permanently discontinued and corticosteroids therapy should be initiated. Once a diagnosis of myocarditis is established, serplulimab should be withheld or permanently discontinued. Myocardial enzymes and cardiac function should be monitored closely for any grade myocarditis (see section 4.2).
If uveitis and other immune-mediated adverse reactions occur at the same time, such as Vogt-Koyanagi-Harada syndrome, systemic corticosteroids should be given to prevent permanent blindness.
Given the mechanism of action of serplulimab, other potential immune-related adverse reactions may occur. Other fatal and life-threatening immune-mediated adverse reactions have been observed in patients treated with serplulimab in clinical trials across doses and tumour types: thrombocytopenia, acute coronary syndrome, myocardial infarction and immune-mediated encephalitis (see section 4.8). For other suspected immune-related adverse reactions, adequate evaluation should be performed to confirm aetiology and exclude other causes. Based on the severity of adverse reactions, serplulimab should be withheld for Grade 2 or 3 immune-related adverse reactions which occur for the first time. For recurrent Grade 3 immune-related adverse reactions (except endocrinopathies) and Grade 4 immune-related adverse reactions, serplulimab must be permanently discontinued. Corticosteroids can be initiated as clinically indicated (see section 4.2).
Infusion-related reactions have been reported in patients receiving serplulimab. Patients should be monitored for clinical signs and symptoms of infusion-related reactions. Patients with Grade 1 infusion-related reactions may continue administration under close monitoring. The rate of infusion should be reduced, or treatment should be interrupted in patients with Grade 2 infusion-related reactions. Antipyretic and antihistamines may be considered. Treatment with serplulimab may be resumed under close monitoring when Grade 2 infusion-related reactions are controlled. For Grade ≥ 3 infusion-related reactions, infusion should be stopped immediately, treatment should be permanently discontinued, and appropriate treatment should be given (see section 4.2).
Patients with the following conditions were excluded from clinical trials: a history of active or prior documented autoimmune disease, patients with active tuberculosis or hepatitis B or C or HIV infection or patients receiving live attenuated vaccine within 28 days prior to serplulimab administration, patients with any active infection requiring systemic anti-infective therapy within 14 days prior to the first dose, history of pneumonitis or interstitial lung disease, patients with active brain metastases, history of significant cardiovascular disease (e.g. myocardial infarction within half a year), a history of hypersensitivity to another monoclonal antibody, systemic immunosuppressive medicinal products within 2 weeks prior to receiving serplulimab.
This medicinal product contains 0.98 mmol (or 22.5 mg) sodium per 10 ml vial, equivalent to 1.1% of the WHO recommended maximum daily intake of 2 g sodium for an adult.
The prescriber must discuss the risks of serplulimab therapy with the patient. The patient will be provided with the patient card with each prescription.
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-related adverse reactions after starting serplulimab (see section 4.4).
Women of childbearing potential should use effective contraception during treatment and for at least 6 months after the last dose of serplulimab.
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.
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.
Studies to evaluate fertility have not been performed. Thus, the effect of serplulimab on male and female fertility is unknown.
Serplulimab has minor influence on the ability to drive and use machines. Because of potential adverse reactions such as fatigue (see section 4.8), patients should be advised to use caution when driving or operating machinery until they are certain that serplulimab does not adversely affect them.
The safety of serplulimab in combination with chemotherapy is based on data in 389 patients with ES-SCLC. The most common adverse reactions were neutropenia (82.8%), leukopenia (74.0%), anaemia (72.8%), thrombocytopenia (56.0%), alopecia (54.2%), nausea (36.2%), hyperlipidaemia (32.1%), decreased appetite (28.3%), hypoproteinaemia (25.4%), and hyponatraemia (25.4%).
The most common Grade ≥ 3 adverse reactions were neutropenia (65.3%), leukopenia (33.7%), thrombocytopenia (23.1%), anaemia (19.8%), hyponatraemia (10.0%), and lymphopenia (5.1%).
The most common serious adverse reactions were thrombocytopenia (9.3%), neutropenia (7.7%), leukopenia (6.7%), pneumonia (3.3%), and hyperglycaemia or diabetes mellitus (2.3%).
The most common immune-related adverse reactions were hypothyroidism (13.1%), hyperthyroidism (10.8%), immune-related skin adverse reactions (7.5%), abnormal liver function (4.1%), immune-related lung disease (3.1%), anaemia (2.8%), malaise (2.1%), hyperglycaemia or diabetes mellitus (1.8%), immune-related colitis (1.8%), and platelet count decreased (1.5%).
Serplulimab was discontinued due to adverse reactions in 5.4% of patients.
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 ASTRUM-005 trial, in which 389 patients were exposed to serplulimab in combination with chemotherapy for a median duration of 22 weeks. See section 5.1 for information about the main characteristics of patients in the pivotal clinical trial.
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 HETRONIFLY* in ASTRUM-005:
| Serplulimab with carboplatin and etoposide | |
|---|---|
| Infections and infestations | |
| Very common | pneumoniaa |
| Common | urinary tract infectionb, respiratory tract infectionc |
| Uncommon | septic shock, skin infection, enteritis infectious, lip infection, meningoencephalitis herpetic |
| Blood and lymphatic system disorders | |
| Very common | neutropenia, leukopenia, anaemia, thrombocytopenia, lymphopenia |
| Common | coagulation function test abnormald, granulocytopenia |
| Uncommon | lymphadenitis |
| Immune system disorders | |
| Common | infusion-related reactione |
| Uncommon | anaphylactic reaction |
| Endocrine disorders | |
| Very common | hypothyroidismf, hyperthyroidism, hyperglycaemia or diabetes mellitusg |
| Common | thyroid function test abnormalh, thyroiditisi |
| Uncommon | adrenal insufficiencyj, other thyroid disorderk, hyperadrenocorticisml, hypophysitis |
| Metabolism and nutrition disorders | |
| Very common | hyperlipidaemia, decreased appetite, hypoproteinaemia, hyperuricaemia, electrolyte imbalancem |
| Common | weight decreased, hypoglycaemia |
| Uncommon | lipoprotein abnormal |
| Psychiatric disorders | |
| Very common | insomnia |
| Nervous system disorders | |
| Common | paraesthesia, headache, dizziness, neuropathy peripheraln |
| Uncommon | immune-mediated encephalitis°, vertigo, neurotoxicity, motor dysfunction |
| Eye disorders | |
| Uncommon | vision blurred |
| Cardiac disorders | |
| Very common | arrhythmiap |
| Common | sinus tachycardia, conduction defectsq, sinus bradycardia, cardiac failurer, N-terminal prohormone brain natriuretic peptide increased |
| Uncommon | cardiomyopathys, myocardial ischaemia, pericardial effusion, myocardial necrosis marker increased, myocarditis |
| Vascular disorders | |
| Common | hypertension, vasculitist |
| Respiratory, thoracic and mediastinal disorders | |
| Very common | cough |
| Common | pneumonitisu, dyspnoea, chest pain |
| Gastrointestinal disorders | |
| Very common | nausea, constipation, abdominal pain, diarrhoea, vomiting |
| Common | dysphagia, flatulence, gastrointestinal disorderv, stomatitis, dyspepsia |
| Uncommon | dry mouth, enteritisw, gastritis, immune-mediated pancreatitis, gingival bleeding |
| Hepatobiliary disorders | |
| Very common | alanine aminotransferase increased, aspartate aminotransferase increased, gamma-glutamyltransferase increased |
| Common | hyperbilirubinaemia, liver injuryx |
| Skin and subcutaneous tissue disorders | |
| Very common | rashy, alopecia |
| Common | pruritus, dermatitisz, hyperhidrosis |
| Uncommon | pigmentation disorder, psoriasis, dry skin |
| Musculoskeletal and connective tissue disorders | |
| Very common | musculoskeletal painaa |
| Common | arthralgia, pain in extremity, musculoskeletal discomfortbb |
| Uncommon | autoimmune myositis, arthritis |
| Not known | myositiscc |
| Renal and urinary disorders | |
| Common | blood urea increased, protein urine present, haematuria, renal injurydd, blood creatinine increased, glycosuria, white blood cells urine positive |
| General disorders and administration site conditions | |
| Very common | pyrexia, asthenia |
| Common | fatigue, malaise, oedemaee |
| Uncommon | chills |
| Investigations | |
| Very common | blood alkaline phosphatase increased |
| Common | myoglobin blood increased, blood creatine phosphokinase increased, troponin increased |
* Adverse reaction frequencies presented in Table 2 may not be fully attributable to HETRONIFLY alone but may contain contributions from the underlying disease or from other medicinal products used in a combination.
The following terms represent a group of related events that describe a medical condition rather than a single event:
a Includes pneumonia, pneumonia fungal.
b Includes urinary tract infection, asymptomatic bacteriuria.
c Includes upper respiratory tract infection, pharyngotonsillitis, tonsillitis.
d Includes activated partial thromboplastin time prolonged, activated partial thromboplastin time, activated partial thromboplastin time shortened, international normalised ratio decreased, prothrombin level increased.
e Includes drug hypersensitivity, infusion-related reaction.
f Includes hypothyroidism, blood thyroid stimulating hormone increased, thyroxine free decreased, central hypothyroidism, tri-iodothyronine decreased.
g Includes hyperglycaemia, diabetes mellitus, diabetic ketoacidosis, blood ketone body increased, glucose tolerance impaired, ketoacidosis.
h Includes blood thyroid stimulating hormone decreased, tri-iodothyronine increased, anti-thyroid antibody positive, thyroglobulin increased, thyroxine increased.
i Includes thyroid disorder, thyroiditis.
j Includes adrenal insufficiency, cortisol decreased.
k Includes euthyroid sick syndrome, ultrasound thyroid abnormal.
l Includes cortisol increased, hyperadrenocorticism.
m Includes hyponatraemia, hypocalcaemia, hypokalaemia, hypomagnesaemia, hypophosphataemia, hypochloraemia, hyperphosphataemia, hyperkalaemia, hypermagnesaemia, hypercalcaemia.
n Includes neuropathy peripheral, peripheral sensorimotor neuropathy, immune-mediated neuropathy**.
° Includes immune-mediated encephalitis, encephalitis autoimmune.
p Includes supraventricular extrasystoles, supraventricular tachycardia, arrhythmia, ventricular extrasystoles, arrhythmia supraventricular, atrial fibrillation, atrial tachycardia, bradyarrhythmia, early repolarisation syndrome, ventricular arrhythmia, electrocardiogram QT prolonged, electrocardiogram repolarisation abnormality, electrocardiogram T wave abnormal.
q Includes atrioventricular block first degree, bundle branch block right, atrial conduction time prolongation, bundle branch block left, defect conduction intraventricular.
r Includes cardiac failure, cardiac failure acute, left ventricular failure.
s Includes cardiomyopathy, metabolic cardiomyopathy.
t Includes phlebitis, phlebitis superficial.
u Includes immune-mediated lung disease, pneumonitis, interstitial lung disease.
v Includes gastrointestinal haemorrhage, gastrointestinal disorder, lower gastrointestinal haemorrhage.
w Includes enteritis, immune-mediated enterocolitis**.
x Includes hepatic function abnormal, drug-induced liver injury, liver injury, immune-mediated hepatitis, immune-mediated hepatic disorder**, hepatic failure**.
y Includes rash, rash maculo-papular, eczema, drug eruption, erythema, skin toxicity.
z Includes autoimmune dermatitis, dermatitis, dermatitis allergic, dermatitis bullous, seborrhoeic dermatitis.
aa Includes back pain, myalgia, musculoskeletal chest pain, spinal pain, neck pain.
bb Includes muscular weakness, musculoskeletal discomfort.
cc Includes myositis**, immune-mediated myositis**.
dd Includes acute kidney injury, renal failure, renal impairment, renal injury.
ee Includes face oedema, oedema peripheral, peripheral swelling, swelling, swelling face.
** Post-marketing event.
Immune-related lung disease occurred in 3.5% of patients, including Grade 3, 4 or 5 in 0.9%, 0.1%, and 0.3% of patients, respectively. The median time to onset was 3.25 months (range: 0.03-34.53 months). The median duration was 1.91 months (range: 0.26-13.34 months). 1.6% of patients received high-dose corticosteroid treatment. Immune-related lung disease led to discontinuation in 1.0% of patients.
Immune-related colitis occurred in 2.4% of patients, including Grade 3 in 0.6% of patients and Grade 5 in 0.1% of patients. The median time to onset was 3.01 months (range: 0.03-20.11 months). The median duration was 0.43 months (range: 0.03-4.40 months). 0.5% of patients received high-dose corticosteroid treatment. Immune-related colitis led to discontinuation in 0.3% of patients.
Hepatitis occurred in 0.7% of patients, including Grade 3 in 0.3% of patients, Grade 4 in 0.2% of patients, and Grade 5 in 0.2% of patients. The median time to onset was 2.48 months (range: 0.43-6.60 months). The median duration was 0.95 months (range: 0.53-1.51 months). 0.2% of patients received high-dose corticosteroid treatment. Hepatitis led to discontinuation in 0.3% of patients. Abnormal liver function occurred in 4.5% of patients, including Grade 3 in 1.0% of patients. The median time to onset was 1.51 months (range: 0.07-29.73 months). The median duration was 1.41 months (range: 0.26-17.54 months). 0.3% of patients received high-dose corticosteroid treatment. Abnormal liver function led to discontinuation in 0.3% of patients.
Immune-related nephritis and renal dysfunction occurred in 2.4% of patients, including Grade 3 in 0.3% of patients and Grade 4 in 0.1% of patients. The median time to onset was 2.78 months (range: 0.23-17.28 months). The median duration was 1.12 months (range: 0.13-5.32 months). 0.2% of patients received high-dose corticosteroid treatment. Immune-related nephritis and renal dysfunction led to discontinuation in 0.2% of patients.
Hypothyroidism occurred in 11.2% of patients, including Grade 3 in 0.1% of patients. The median time to onset was 3.84 months (range: 0.62-34.10 months). The median duration was 2.76 months (range: 0.53-7.49 months). 5.9% of patients received thyroid hormone replacement therapy. No patients discontinued serplulimab due to hypothyroidism.
Hyperthyroidism occurred in 6.3% of patients, and there were no Grade ≥ 3 hyperthyroidism. The median time to onset was 1.79 months (range: 0.69-31.18 months). The median duration was 1.41 months (range: 0.07-4.21 months). No patients discontinued serplulimab due to hyperthyroidism.
Thyroiditis occurred in 0.7% of patients, and there were no Grade ≥ 3 thyroiditis. The median time to onset was 5.65 months (range: 1.94-13.50 months). The median duration was 5.93 months (range: 0.56-11.30 months). 0.2% of patients received thyroid hormone replacement therapy. No patients discontinued serplulimab due to thyroiditis.
Adrenal gland disorders occurred in 0.3% of patients, all of which were Grade 2. The median time to onset was 5.78 months (range: 5.75-6.93 months). No patients discontinued serplulimab due to adrenal gland disorders.
Pituitary disorders occurred in 0.9% of patients, including Grade 3 in 0.2% of patients. The median time to onset was 6.97 months (range: 1.41-20.53 months). The median duration was 2.43 months.
0.3% of patients received high-dose corticosteroid treatment. Pituitary disorders led to discontinuation in 0.2% of patients.
Diabetes mellitus/hyperglycaemia occurred in 1.0% of patients, including Grade 3 in 0.5% of patients and Grade 4 in 0.1% of patients. The median time to onset was 4.09 months (range: 0.69-11.10 months). The median duration was 2.96 months. 0.6% of patients received insulin replacement therapy. Diabetes mellitus/hyperglycaemia led to discontinuation in 0.1% of patients.
Immune-related skin adverse reactions occurred in 8.7% of patients, including Grade 3 in 0.8% of patients. The median time to onset was 2.10 months (range: 0.03-30.52months). The median duration was 0.82 months (range: 0.07-12.39 months). 1.4% of patients received high-dose corticosteroid treatment. Immune-related skin adverse reactions led to discontinuation in 0.4% of patients.
Immune-related pancreatitis occurred in 1.1% of patients, including Grade 3 in 0.3% of patients, Grade 4 in 0.2% of patients and Grade 5 in 0.1% of patients. The median time to onset was 2.30 months (range: 0.23-12.42 months). The median duration was 0.76 months (range: 0.16-10.12 months). 0.2% of patients received high-dose corticosteroid treatment. Immune-related pancreatitis led to discontinuation in 0.2% of patients.
Immune-related myocarditis occurred in 0.6% of patients, including Grade 3 in 0.2% of patients and Grade 5 in 0.1% of patients. The median time to onset was 1.87 months (range: 0.26-25.36 months). The median duration was 0.89 months (range: 0.72-4.57 months). 0.3% of patients received high-dose corticosteroid treatment. Immune-related myocarditis led to discontinuation in 0.2% of patients.
Immune-related uveitis occurred in 0.1% of patients, which was Grade 1. The time to onset was 6.90 months. The duration of immune-related uveitis was 1.35 months. The event resolved for the patient.
Other clinically significant immune-related adverse reactions reported in patients who received serplulimab were as follows. Severe or fatal cases have been reported for some of these adverse reactions.
Blood and lymphatic system: anaemia, leukopenia, thrombocytopenia, neutropenia.
Nervous system: dizziness, immune-mediated encephalitis, neuropathy peripheral.
Eye disorders: vision blurred.
Cardiac/vascular: acute coronary syndrome, myocardial infarction, cardiac failure acute, cardiotoxicity, troponin increased.
Respiratory, thoracic and mediastinal: dyspnoea, chronic obstructive pulmonary disease, respiratory failure.
Gastrointestinal: mouth ulceration, vomiting, proctitis.
General disorders and administration site conditions: asthenia, fatigue, pyrexia.
Other: panic disorder, tinnitus, cholangitis acute, sepsis, cortisol decreased, blood alkaline phosphatase increased, electrolyte imbalance.
Infusion-related reactions occurred in 1.4% of patients, including Grade 3 in 0.2% of patients and Grade 4 in 0.1% of patients. The median time to onset was 1.02 months (range: 0.03-9.86 months). The median duration was 0.07 months (range: 0.03-0.53 months). No patients discontinued serplulimab due to infusion-related reactions.
The proportions of patients who experienced a shift from baseline to a Grade ≥ 3 laboratory abnormality were as follows: 0.6% for platelet count decreased, 0.4% for neutrophil count decreased, 0.3% for blood creatine phosphokinase increased, 0.2% for white blood cell count decreased, 0.1% for blood lactate dehydrogenase increased, and 0.1% for blood cholesterol increased.
No overall differences in safety were reported between elderly (≥65 years) and younger patients. Data for patients ≥75 years of age are too limited to draw conclusions on this population.
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via the national reporting system listed in Appendix V.
In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products, except those mentioned in section 6.6. HETRONIFLY should not be infused concomitantly in the same intravenous line with other medicinal products.
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