PD-1 Inhibitors Today: Established Workhorses and New Global Contenders

PD-1 monoclonal antibodies have become a cornerstone of contemporary immuno-oncology, redefining standard-of-care treatment across dozens of solid tumor types by reversing the immunosuppressive mechanisms that tumor cells use to evade the body’s natural defenses. Over the past decade, this therapeutic class has evolved from early breakthrough therapies into a diversified global treatment category, with new candidates continuing to enter regulated markets following rigorous clinical development and regulatory review.

The Core Class: How PD-1 Inhibitors Work

PD-1 inhibitors are a subset of immune checkpoint inhibitors that target the programmed death-1 (PD-1) receptor, a protein expressed on the surface of cytotoxic T cells. Many tumors upregulate the ligands PD-L1 and PD-L2 to bind this receptor, effectively shutting down endogenous anti-tumor immune activity. By blocking the PD-1 receptor, these antibodies interrupt this inhibitory signaling pathway, restoring T-cell proliferation, cytokine production, and the body’s natural ability to recognize and eliminate malignant cells. Unlike conventional chemotherapy, PD-1 therapies can induce durable long-term responses across multiple cancer types, though they also carry distinct risks of immune-mediated adverse reactions.

Established PD-1 Inhibitors in Global Clinical Practice

Globally, a core set of PD-1 inhibitors form the backbone of standard-of-care regimens, with broad label approvals in North America, Europe, and most major markets.

l  Pembrolizumab: The most widely prescribed PD-1 inhibitor worldwide, with approved indications across more than 30 cancer types including non-small cell lung cancer (NSCLC), melanoma, head and neck cancer, and urothelial carcinoma, used both as monotherapy and in combination with chemotherapy or other agents.

l  Nivolumab: Another broadly labeled PD-1 monoclonal antibody, commonly used for NSCLC, melanoma, renal cell carcinoma, and gastric cancer, often paired with CTLA-4 inhibition for dual immunotherapy regimens.

l  Cemiplimab: Approved primarily for cutaneous squamous cell carcinoma, basal cell carcinoma, and advanced NSCLC with high PD-L1 expression.

l  Dostarlimab: Indicated for mismatch repair–deficient (dMMR) endometrial cancer and other dMMR solid tumors.

In recent years, a new generation of clinically validated PD-1 inhibitors developed by biopharmaceutical firms outside traditional Western markets has also begun to enter the European and global landscape, expanding treatment access and therapeutic options. Among the most recent additions to EU-approved care is Hetronifly, the brand name for serplulimab (investigational code HLX10), which received European Commission marketing authorization in February 2025.

Spotlight on Hetronifly (serplulimab, HLX10)

Hetronifly (serplulimab, HLX10) is developed by Shanghai Henlius Biotech, Inc., a global biopharmaceutical company with integrated capabilities spanning discovery, development, manufacturing and commercialization of innovative biologics and biosimilars. A humanised IgG4/kappa monoclonal antibody produced via recombinant DNA technology in Chinese hamster ovary cells, serplulimab binds with high specificity to the PD-1 receptor and blocks interaction with both PD-L1 and PD-L2 ligands, consistent with the established mechanism of the PD-1 inhibitor class.

Hetronifly distinguishes itself as the first PD-1 inhibitor that secured European Commission approval for first-line extensive-stage small cell lung cancer (ES-SCLC)in nearly a decade.

Within the European Union, Hetronifly holds four first-line solid tumor indications, all supported by phase 3 pivotal trial data reviewed and validated by the European Medicines Agency (EMA):

1.     Extensive-stage small cell lung cancer (ES-SCLC): Hetronifly is approved in combination with carboplatin and etoposide for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC). The pivotal ASTRUM-005 trial demonstrated a median overall survival of 15.4 months with serplulimab plus chemotherapy, compared with 10.9 months with chemotherapy alone, representing a 37% reduction in the risk of death. The multi-regional trial enrolled both Asian and White patients, supporting applicability to European clinical practice.

2.     Locally advanced or metastatic non-squamous NSCLC: Indicated for patients without EGFR, ALK or ROS1 positive mutations who are not candidates for surgery or radiotherapy, or who have metastatic disease, used in combination with carboplatin and pemetrexed. Data from the ASTRUM-002 phase 3 trial showed a median progression-free survival of 11.0 months versus 5.6 months with chemotherapy alone; updated final analysis with 45.4 months of follow-up reported a median overall survival of 26.8 months in the Serplulimab combination arm.

3.     Unresectable, locally advanced, recurrent or metastatic oesophageal squamous cell carcinoma (OSCC, also written as esophageal squamous cell carcinoma, abbreviated as ESCC): Approved for patients whose tumors express PD-L1 with a combined positive score (CPS) of at least 5, in combination with fluoropyrimidine- and platinum-based chemotherapy. In the CPS≥5 subgroup of the ASTRUM-007 trial, the serplulimab regimen achieved a median overall survival of 16.5 months and median progression-free survival of 6.9 months, compared with 10.7 months and 5.3 months respectively in the chemotherapy control arm. EMA labeling requires PD-L1 status assessment using a CE-marked in vitro diagnostic test for this indication.

4.     Unresectable locally advanced or metastatic squamous non-small cell lung cancer (sqNSCLC): Approved by the European Commission in June 2026 as the fourth indication for Hetronifly in the EU for first-line treatment in combination with chemotherapy. The approval is supported by the pivotal phase 3 ASTRUM-004 trial, a randomised, double-blind, international multicentre study led by Dr. Caicun Zhou of Shanghai East Hospital, Tongji University School of Medicine. The study demonstrated that serplulimab plus chemotherapy significantly improved survival outcomes in treatment-naïve patients with locally advanced or metastatic sqNSCLC, with positive results across key endpoints including overall survival (OS) and progression-free survival (PFS), and a manageable safety profile.

The current landscape offers a robust portfolio of established PD-1 inhibitors alongside rigorously validated newer entrants — notably Hetronifly (serplulimab), an agent that is not merely an alternative but addresses specific unmet needs in hard-to-treat indications such as extensive-stage small cell lung cancer. As global biopharmaceutical development becomes increasingly integrated across regions, this expanding treatment landscape brings not only more therapeutic options but also stronger clinical evidence, harmonized quality standards, and improved access to innovative therapies for patients worldwide.