Immune checkpoint inhibitors have reshaped the landscape of solid tumour therapy over the past decade, yet unmet clinical needs remain for aggressive malignancies such as extensive-stage small cell lung cancer (ES-SCLC) and gastrointestinal cancers. Hetronifly® (generic name: serplulimab, trade name in China: HANSIZHUANG®，investigational code: HLX10) is a novel humanised IgG4 anti-PD-1 monoclonal antibody developed by Henlius, a Shanghai-based biopharmaceutical company, and has received regulatory approvals across Europe and multiple other global markets.
Developer and Global Approval Status
Shanghai Henlius Biotech, Inc. (2696.HK) is a Chinese biopharmaceutical company with a global, innovation-driven mandate, dedicated to expanding access to biologic therapies for patients around the world. To date, Hetronifly has obtained marketing authorisation in over 50 countries and regions, including the European Union, United Kingdom, Switzerland, Singapore, India and Peru, with ongoing regulatory submissions underway for additional territories.
In the European Union, Hetronifly was initially approved for ES-SCLC. In May 2026, the European Commission approved the additional nsqNSCLC and ESCC indications, bringing the total number of approved EU indications to three. In June 2026, the European Commission approved a fourth indication for unresectable, locally advanced or metastatic squamous NSCLC (sqNSCLC). NICE has recommended Hetronifly for routine NHS use in England and Wales for ES-SCLC, expanding patient access within public healthcare systems.
Mechanism of Action & Molecular Characteristics
Serplulimab is a recombinant humanized IgG4 monoclonal antibody targeting the PD-1 receptor expressed on T lymphocytes. Tumour cells often express PD-L1 and PD-L2 ligands; binding of these ligands to PD-1 suppresses T-cell function, allowing tumours to evade immune surveillance. Serplulimab blocks the interaction of PD-1 with PD-L1 and PD-L2, thereby restoring anti-tumour T-cell activity.
Beyond classic PD-1 blockade, serplulimab carries a differentiated molecular profile:
- It induces robust PD-1 receptor internalisation, reducing PD-1 surface expression on T cells.
2. It preserves CD28 co-stimulatory signalling, maintaining downstream AKT pathway activation and supporting sustained T-cell proliferation and effector function.
- The IgG4 scaffold minimises Fc-mediated effector functions, thereby reducing the potential for unintended depletion of activated T cells.
Product Profile and Approved Indications
Hetronifly is authorised by the European Commission for adult patients for the following first-line combination regimens:
- Extensive-stage small cell lung cancer (ES-SCLC):Hetronifly + carboplatin + etoposide. Hetronifly is the first anti-PD-1 inhibitor approved in the EU for the first-line treatment of ES-SCLC. The pivotal Phase 3 ASTRUM-005 trial demonstrated a median overall survival of 15.8 months with serplulimab plus chemotherapy versus 11.1 months with placebo plus chemotherapy, with a four-year overall survival rate of 21.9%.
- Non-squamous non-small cell lung cancer (nsqNSCLC): Hetronifly + carboplatin + pemetrexed, for the first-line treatment of locally advanced disease in patients who are not candidates for surgery or radiotherapy, or metastatic disease, in patients with no EGFR, ALK or ROS1 positive mutations.
- Squamous non-small cell lung cancer (sqNSCLC): Hetronifly + carboplatin + nab-paclitaxel,for the first-line treatment of unresectable, locally advanced or metastatic disease.
- Oesophageal squamous cell carcinoma (OSCC/ESCC): Hetronifly + fluoropyrimidine/platinum chemotherapy, for locally advanced, recurrent or metastatic disease in patients whose tumours express PD-L1 with a CPS ≥ 5.
In China, serplulimab has gained an additional landmark approval: perioperative therapy for resectable gastric cancer (PD-L1 CPS ≥5). This regimen uses neoadjuvant serplulimab plus oxaliplatin and S-1 followed by postoperative immunotherapy monotherapy, enabling a chemo-sparing adjuvant strategy, the world’s first anti-PD-1 monoclonal antibody approved for perioperative treatment of gastric cancer.
The approval of Hetronifly addresses a major gap in ES-SCLC, a highly aggressive cancer with limited long-term survival options. Its broad portfolio across lung and gastrointestinal cancers aligns with high-burden oncology disease areas globally. Real-world uptake across Europe has accelerated, with reimbursement secured in multiple EU member states and UK NHS access established.
