What are the indications and uses of serplulimab in different types of cancer, including non-small cell lung cancer and renal cell carcinoma?

Serplulimab Indications in Cancer

Primary Approved Indication

Serplulimab is approved in China for extensive-stage small cell lung cancer (ES-SCLC) as first-line treatment in combination with chemotherapy, and for advanced microsatellite instability-high (MSI-H) solid tumors after failure of standard treatments. 1, 2

Extensive-Stage Small Cell Lung Cancer (ES-SCLC)

First-Line Treatment

• Serplulimab combined with platinum-etoposide chemotherapy is the primary indication, demonstrating superior efficacy compared to chemotherapy alone in the ASTRUM-005 phase III trial. 1
• The combination achieved median overall survival of 15.4 months versus 10.9 months with chemotherapy alone (HR not specified), median progression-free survival of 5.7 months versus 4.3 months, and objective response rate of 80.2% versus 70.4%. 1
• One-year survival rate reached 61% with serplulimab versus 48% with placebo. 1
• This indication positions serplulimab as an alternative to durvalumab, which is the established standard with median OS of 13.0 months versus 10.3 months for chemotherapy alone (HR 0.73,95% CI 0.59-0.91). 3

Treatment Protocol

• Serplulimab blocks PD-1 receptors on T cells, preventing interaction with PD-L1/PD-L2 ligands and enabling enhanced anti-tumor immune responses. 1
• The mechanism differs from anti-CTLA-4 agents by acting at the T cell-tumor interface rather than the T cell-dendritic cell interface. 1

Advanced Squamous Non-Small Cell Lung Cancer (NSCLC)

First-Line Treatment

• Serplulimab combined with nab-paclitaxel and carboplatin is approved for previously untreated stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations (EGFR/ALK). 4
• The ASTRUM-004 phase III trial (n=537) demonstrated median OS improvement with serplulimab-chemotherapy versus placebo-chemotherapy (HR 0.73,95% CI 0.58-0.93; p=0.010). 4
• Progression-free survival showed substantial benefit (HR 0.53,95% CI 0.42-0.67). 4
• This indication aligns with established PD-1 inhibitors like pembrolizumab, which is approved for first-line treatment of metastatic squamous NSCLC in combination with carboplatin and paclitaxel or nab-paclitaxel. 5

Microsatellite Instability-High (MSI-H) Solid Tumors

Second-Line and Beyond

• Serplulimab received approval in China for adult patients with advanced unresectable or metastatic MSI-H solid tumors that have failed previous standard treatments. 2
• This indication follows the precedent established by pembrolizumab, which demonstrated 40% objective response rate in dMMR colorectal cancer and 71% in dMMR non-colorectal carcinomas, with MSI serving as a predictive marker across tumor types. 5
• The approval is tissue-agnostic, meaning it applies regardless of the primary tumor site, as long as MSI-H status is confirmed. 5, 2

Metastatic or Recurrent Solid Tumors (Investigational)

Phase I Evidence

• Serplulimab demonstrated preliminary efficacy in a phase I dose-escalation study of 29 patients with stage IV solid tumors (34.5% with lung cancer). 6
• Objective response rate was 8.0% and disease control rate was 60.0% across various solid tumor types. 6
• The maximum tolerated dose was not reached at doses up to 10.0 mg/kg every 2 weeks, suggesting a favorable therapeutic window. 6

Mechanistic Advantages and Combination Potential

Distinctive Molecular Properties

• Serplulimab robustly induces PD-1 receptor endocytosis while fostering weaker PD-1-CD28 cis interactions compared to pembrolizumab and nivolumab. 7
• This mechanism mitigates dephosphorylation of CD28 by SHP2, facilitating sustained T cell activation. 7
• When combined with anti-TIGIT or anti-LAG3 inhibitors, serplulimab demonstrates superior tumor killing efficacy compared to pembrolizumab combinations by reducing Treg populations and augmenting effector and memory T cells. 7

Safety Profile Across Indications

Immune-Related Adverse Events

• Grade 3-4 adverse events occur in approximately 13.8-35.2% of patients, with immune-related adverse events (irAEs) requiring vigilant monitoring. 1, 6, 4
• The incidence of irAEs with serplulimab is ≤30% for any grade and ≤20% for grade ≥3 severity, consistent with other anti-PD-1 agents. 1
• Treatment-related mortality ranges from 1.5-5%, emphasizing the need for multidisciplinary toxicity management. 1
• Early recognition and prompt corticosteroid intervention is critical for managing irAEs. 1

Specific Toxicity Data

• In ES-SCLC, predominantly grade 1-2 adverse events were observed with manageable safety profile. 1
• In squamous NSCLC, grade ≥3 serplulimab-related adverse events occurred in 35.2% versus 32.4% with placebo-chemotherapy. 4
• Most common treatment-emergent adverse events include nausea (24.1%), with no notable differences between dose cohorts. 6

Contraindications and Precautions

Absolute Contraindications

• Active autoimmune disease requiring systemic immunosuppression. 3
• History of grade ≥2 pneumonitis from prior immunotherapy. 3
• Interstitial lung disease or active pneumonitis. 3

Relative Contraindications

• Patients with EGFR mutations or ALK rearrangements should receive targeted therapy first, as no benefit for adding immunotherapy to chemotherapy was observed in these populations. 5
• Never smokers (<100 cigarettes in lifetime) may derive less benefit from PD-1 monotherapy and should be prioritized for combination approaches. 5