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First-line serplulimab plus chemotherapy with or without HLX04 versus chemotherapy in locally advanced or metastatic non-squamous non-small-cell lung cancer (ASTRUM-002): a randomised, double-blind, multicentre phase 3 trial.

The Lancet. Respiratory medicine2025-12-08PubMed
Total: 78.0Innovation: 6Impact: 8Rigor: 9Citation: 8

Summary

Serplulimab plus chemotherapy significantly prolonged PFS versus chemotherapy alone in first-line non-squamous NSCLC (HR 0.55). Adding bevacizumab biosimilar HLX04 to serplulimab plus chemotherapy did not further improve PFS. Serious treatment-related adverse events were more frequent with immunotherapy-containing regimens.

Key Findings

  • Serplulimab + chemotherapy improved PFS vs chemotherapy alone (HR 0.55, 95% CI 0.43–0.69; p<0.0001)
  • Adding HLX04 to serplulimab + chemotherapy did not significantly improve PFS (HR 0.86; p=0.25)
  • Serious treatment-related adverse events: 39% (A), 37% (B), 24% (C); grade ≥3 TRAEs: 71% (A), 66% (B), 57% (C)

Clinical Implications

For EGFR/ALK/ROS1–negative non-squamous NSCLC, serplulimab plus pemetrexed-carboplatin is a viable first-line option; routine addition of bevacizumab is not supported. Monitor for higher rates of serious treatment-related adverse events.

Why It Matters

A large, double-blind phase 3 trial establishes serplulimab plus chemotherapy as an effective first-line option and clarifies that bevacizumab addition offers no incremental benefit, informing regimen selection and resource allocation.

Limitations

  • Population enrolled exclusively in China; generalizability beyond this setting requires caution
  • Overall survival and biomarker analyses not detailed in abstract

Future Directions

Report OS, quality-of-life, and biomarker-defined subgroups; compare against established PD-1/PD-L1 regimens and evaluate real-world safety.

Study Information

Study Type
RCT
Research Domain
Treatment
Evidence Level
I - Double-blind, multicentre phase 3 randomized controlled trial
Study Design
OTHER