Serplulimab

Serplulimab is a humanised monoclonal antibody and immune checkpoint inhibitor that targets programmed cell death protein 1 (PD-1), a receptor involved in regulating immune responses. Some cancer cells use the PD-1 pathway to reduce the activity of immune cells that might otherwise recognise and attack them. By blocking PD-1, serplulimab can help restore antitumour immune activity. It is administered by intravenous infusion and is used in combination with chemotherapy for selected cancers, with approved indications varying by country. These include first-line treatment of extensive-stage small-cell lung cancer and, in the European Union, certain forms of non-small-cell lung cancer and oesophageal squamous cell carcinoma. Serplulimab is not a conventional chemotherapy medicine; however, it is often given alongside chemotherapy to improve treatment outcomes. As with other PD-1 inhibitors, it can cause immune-related adverse effects when the activated immune system affects healthy organs, including the lungs, bowel, liver, kidneys, skin and endocrine glands. Treatment therefore requires specialist supervision, assessment of the patient's medical history, and monitoring for toxicity and treatment response. The appropriate regimen depends on the cancer type, stage, combination medicines and current local prescribing information.

Serplulimab was developed as an immune checkpoint inhibitor designed to block PD-1 and help the immune system recognise and attack cancer cells. Its first approval was granted by China's National Medical Products Administration (NMPA) on 25 March 2022 for adults with advanced, unresectable or metastatic microsatellite instability-high (MSI-H) solid tumours that had progressed after standard treatment. Further approvals in China included selected lung and oesophageal cancers. In the European Union, the European Commission authorised Hetronifly on 3 February 2025. European indications include first-line treatment of extensive-stage small-cell lung cancer and specified forms of non-small-cell lung cancer and PD-L1-positive oesophageal squamous cell carcinoma, in combination with appropriate chemotherapy. The ASTRUM-005 phase 3 trial evaluated serplulimab with carboplatin and etoposide in previously untreated extensive-stage small-cell lung cancer and demonstrated improved overall survival compared with chemotherapy alone. Other clinical programmes have assessed serplulimab in non-small-cell lung cancer and oesophageal cancer. Regulatory approvals differ between countries; US orphan-drug designation or permission to conduct a clinical trial should not be interpreted as FDA marketing approval.

Serplulimab is used in combination with chemotherapy for selected cancers, according to local regulatory approval. In the European Union, it is indicated with carboplatin and etoposide for first-line treatment of adults with extensive-stage small-cell lung cancer. It is also indicated with carboplatin and pemetrexed for eligible adults with previously untreated non-squamous non-small-cell lung cancer that is locally advanced and unsuitable for surgery or radiotherapy, or metastatic, without positive EGFR, ALK or ROS1 alterations. For selected adults with previously untreated squamous non-small-cell lung cancer that is unresectable, locally advanced or metastatic, it is used with carboplatin and nab-paclitaxel. Another European indication is first-line treatment of unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma when the tumour has a PD-L1 combined positive score of at least 5; it is given with fluoropyrimidine- and platinum-based chemotherapy. China has also approved serplulimab for specified patients with MSI-H solid tumours. The precise indication, line of treatment, biomarker requirements and chemotherapy combination must be confirmed against the current local product information.

Serplulimab is administered by intravenous infusion under the supervision of a physician experienced in cancer treatment. In the European Union, the recommended dose for small-cell lung cancer and the specified non-small-cell lung cancer indications is 4.5 mg/kg every three weeks. For oesophageal squamous cell carcinoma, the recommended dose is 3 mg/kg every two weeks. The chemotherapy schedule varies by cancer type: induction treatment may include several cycles of combination chemotherapy, followed by continued serplulimab and, where appropriate, maintenance chemotherapy. Treatment generally continues while the patient is benefiting and tolerating therapy, until disease progression or unacceptable toxicity, subject to the applicable treatment protocol. Dose escalation or reduction is not recommended in the European product information; treatment may instead be withheld or permanently discontinued when adverse reactions require it. Infusion preparation, administration time and handling must follow the product information and institutional procedures. Patients should receive treatment in an appropriately equipped clinical setting, where infusion reactions and other serious adverse effects can be assessed and managed.

Common side effects depend on the cancer being treated and the chemotherapy medicines used alongside serplulimab. Reported effects include reduced white blood cell and neutrophil counts, anaemia, low platelet counts, nausea, vomiting, reduced appetite, weakness and changes in liver enzyme levels. Thyroid dysfunction, including hypothyroidism and hyperthyroidism, may occur because serplulimab affects immune regulation. Patients may also experience infusion-related reactions or symptoms associated with the accompanying chemotherapy. The severity of adverse effects varies, and some may be caused by chemotherapy rather than serplulimab alone. Regular clinical assessment and laboratory monitoring help clinicians identify complications early. Patients should report new, persistent or worsening symptoms promptly rather than attempting to manage potentially serious effects without medical advice.

Serplulimab can cause immune-related adverse reactions when immune activity affects healthy tissues. These may include inflammation of the lungs (pneumonitis), bowel inflammation (colitis), hepatitis, kidney inflammation, skin reactions and endocrine disorders involving the thyroid, adrenal glands or pituitary gland. Some reactions can be severe or life-threatening and may occur during treatment or after the last dose. Persistent cough, shortness of breath, severe diarrhoea, abdominal pain, jaundice, marked weakness or unusual changes in thirst or urination require prompt medical assessment. Severe infusion-related or allergic reactions are also possible. Treatment may need to be withheld, and corticosteroids or other immunosuppressive treatment may be required for significant immune-related toxicity. Depending on the type and severity of the reaction, permanent discontinuation may be necessary. Serplulimab should not be used in patients with a known serious hypersensitivity to the active substance or relevant formulation components. Decisions about interruption or discontinuation should follow the current prescribing information and specialist assessment.

Before treatment, clinicians should review the patient's medical history, current medicines, previous immune-related disorders, organ function and any active or recent infections. Baseline assessments commonly include a complete blood count, liver and kidney function tests, thyroid function and other investigations guided by the patient's condition and treatment regimen. Patients with autoimmune disease, organ transplantation, previous severe immune-related toxicity or significant lung or liver disease require an individual assessment of risks and benefits. Vaccination status should be reviewed before treatment, and live vaccines should generally be avoided during therapy unless specifically advised by the treating specialist. As serplulimab is a monoclonal antibody, classic metabolic drug interactions involving liver enzymes are not generally expected; however, interactions in clinical practice may arise from concomitant immunosuppressive medicines, chemotherapy or treatments used to manage immune-related adverse reactions. Pregnancy and breastfeeding should be discussed with the oncology team, as treatment decisions require consideration of potential risks and the available evidence. Patients should inform every healthcare professional involved in their care that they are receiving a PD-1 inhibitor.

Confirm the locally approved indication, treatment line, chemotherapy combination and any required tumour biomarker testing before starting serplulimab. For oesophageal squamous cell carcinoma under the European indication, verify the PD-L1 combined positive score using an appropriately validated test. Record baseline symptoms, performance status, blood counts, liver and kidney function, and thyroid function; consider additional tests based on comorbidities and the chemotherapy regimen. Review each cycle for signs of pneumonitis, colitis, hepatitis, endocrine dysfunction, skin toxicity and infusion reactions, and provide clear instructions on symptoms that require urgent review. Explain that immune-related toxicities can arise after treatment has stopped. During administration, follow the approved dilution, infusion-rate, compatibility and handling instructions, and ensure that appropriate monitoring and emergency support are available. When a new symptom develops, assess whether it may reflect cancer progression, infection, chemotherapy toxicity or an immune-related adverse reaction. Coordinate care with the oncology team and relevant specialists when organ-specific toxicity is suspected. Dose delays and permanent discontinuation should follow the current product information rather than informal dose reduction.