Serplulimab
Overview
Serplulimab is a humanized IgG4 monoclonal antibody that targets the programmed death‑1 (PD‑1) receptor on T cells. By binding to PD‑1, it blocks interaction with its ligands PD‑L1 and PD‑L2, thereby lifting the inhibitory “checkpoint” that restrains T‑cell activation. This restores T‑cell mediated immune response against tumor cells, promoting immune‑mediated tumor destruction. Serplulimab is given by intravenous infusion, and is used in combination with chemotherapy in certain cancers to boost anti-tumor immune activity.
Background and Date of Approval
Serplulimab was developed by Shanghai Henlius Biotech as a novel anti‑PD‑1 antibody. The drug received its first regulatory approval in March 2022 in China for the treatment of unresectable or metastatic microsatellite instability–high (MSI‑H) solid tumors in adults whose disease had progressed after prior treatment. Over time, additional approvals followed in China, including for squamous non‑small cell lung cancer, esophageal squamous cell carcinoma, and non-squamous NSCLC. In 2025, the European Commission granted marketing authorization for Serplulimab under the trade name Hetronifly® in combination with carboplatin and etoposide for first-line treatment of extensive‑stage small cell lung cancer across the EU. The approval was based on data from the phase 3 ASTRUM‑005 study, which demonstrated significant clinical benefit when serplulimab was added to chemotherapy.
Uses
Serplulimab is indicated for adult patients with MSI‑H or mismatch repair deficient (dMMR) solid tumors that have progressed after prior therapy. It is also indicated in first‑line therapy, in combination with chemotherapy, for extensive‑stage small cell lung cancer. Additional approved indications in some regions include squamous and non‑squamous non-small cell lung cancer, as well as esophageal squamous cell carcinoma. Use in a given patient depends on tumor molecular profile, prior treatments, and local regulatory approval.
Administration
Serplulimab is administered by intravenous infusion. For extensive-stage small cell lung cancer, the typical regimen involves dosing every three weeks during induction, followed by maintenance dosing every six weeks, as per the approved protocol. Treatment continues until disease progression or unacceptable toxicity. Before initiating therapy, baseline assessments including tumor molecular status and organ function are recommended, and ongoing monitoring is required during treatment.
Side Effects
Commonly observed side effects of Serplulimab include fatigue, nausea, decreased appetite, rash, pruritus, diarrhea, and general weakness. These reflect its immune‑activating mechanism, and many adverse effects stem from immune activation rather than direct cytotoxicity.
Warnings
Because Serplulimab enhances immune activity, serious immune‑mediated toxicities can occur. These may include pneumonitis, colitis, hepatitis, endocrinopathies (such as thyroid dysfunction), nephritis, and skin auto‑immune reactions. These events can be severe or life-threatening, and prompt recognition, treatment, and discontinuation may be required. Patients with pre‑existing autoimmune conditions or compromised organ function warrant careful evaluation before initiation.
Precautions
Before starting Serplulimab, it is important to assess baseline organ function, including liver, kidney, lung, and endocrine systems. Use of concurrent immunosuppressive therapies may reduce its efficacy or increase the risk of adverse events and should be evaluated carefully. Live vaccines are generally avoided during therapy. While classic small‑molecule drug interactions are unlikely, any therapy that affects immune response should be managed with caution. During treatment, clinicians should monitor for new or worsening symptoms suggestive of immune‑related toxicity.
Expert Tips
Counsel patients about how Serplulimab works by boosting immune response and about the profile of immune-related side effects. Arrange baseline tests for organ function and tumor markers before therapy. Manage infusion logistics, ensuring proper handling and storage as per biologic product guidelines. Schedule regular follow-ups to detect immune‑mediated toxicities early. If combining with chemotherapy, coordinate dosing and supportive care carefully.