Serplulimab Plus Chemotherapy Wins EU Approval for Treatment-Naive ES-SCLC

The European Commission has approved the anti–PD-1 monoclonal antibody serplulimab (Hetronifly) in combination with carboplatin and etoposide for the frontline treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).1

This regulatory decision was primarily supported by findings from the double-blind, international, multicenter phase 3 ASTRUM-005 trial (NCT04063163), in which serplulimab plus chemotherapy elicited a significant overall survival (OS) benefit compared with placebo plus chemotherapy in the first-line setting in patients with ES-SCLC.2 At a median follow-up of 12.3 months (range, 0.2-24.8), the median OS was 15.4 months (95% CI, 13.3-not evaluable) with serplulimab vs 10.9 months (95% CI, 10.0-14.3) with placebo (HR, 0.63; 95% CI, 0.49-0.82; P < .001). The estimated 1-year OS rate was 60.7% (95% CI, 54.9%-66.0%) in the serplulimab arm vs 47.8% (95% CI, 39.6%-55.6%) in the placebo arm. The estimated 2-year OS rates in these respective arms were 43.1% (95% CI, 34.1%-51.7%) and 7.9% (95% CI, 0.7%-27.2%).

“The approval of serplulimab in the European Union represents another significant step forward in our mission to benefit patients worldwide,” Jason Zhu, MD, MBA, executive director and chief executive officer of Henlius Biotech, stated in a news release.1 “This milestone not only underscores our leadership in innovative drug development and global strategy, but also brings new hope to ES-SCLC patients in Europe and beyond. Moving forward, we will continue to collaborate with our partners to enhance the accessibility of advanced therapies and work together to make a meaningful difference in patients’ lives.”

Between September 12, 2019, and April 27, 2021, ASTRUM-005 randomly assigned 585 patients with ES-SCLC who had not previously received systemic therapy 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously (IV) every 3 weeks, in combination with IV carboplatin plus etoposide every 3 weeks for a maximum of 12 weeks.2

OS served as the trial’s primary end point. Key secondary end points included progression-free survival (PFS) and adverse effects (AEs).

The median PFS, as assessed by an independent radiology review committee, was 5.7 months (95% CI, 5.5-6.9) with serplulimab vs 4.3 months (95% CI, 4.2-4.5) with placebo (HR, 0.48; 95% CI, 0.38-0.59). The objective response rates in these respective groups were 80.2% (95% CI, 75.9%-84.1%) and 70.4% (95% CI, 63.5%-76.7%). Among patients with complete or partial response, the median duration of response was 5.6 months (95% CI, 4.2-6.8) in the serplulimab arm vs 3.2 months (95% CI, 2.9-4.2) in the placebo arm.

Treatment-emergent AEs (TEAEs) occurred in 95.6% of patients in the serplulimab arm (grade ≥ 3, 82.5%) vs 97.4% of those in the placebo arm (grade ≥ 3, 80.1%). Treatment-related AEs (TRAEs) were reported in 69.9% and 56.1% of patients in these respective arms. TRAEs of grade 3 or higher were reported in 33.2% of patients in the serplulimab arm vs 27.6% of those in the placebo arm. The most common grade 3 or higher TRAEs were decreased neutrophil counts (serplulimab arm, 14.1%; placebo arm, 13.8%), decreased white blood cell counts (8.5%; 8.7%), decreased platelet counts (6.2%; 8.2%), and anemia (5.4%; 5.6%).

TEAEs led to treatment discontinuation in 8.0% of patients in the serplulimab arm vs 7.7% of those in the placebo arm. TRAEs led to treatment discontinuation in 4.9% and 4.1% of patients in these respective arms. Deaths due to TEAEs were reported in 7.7% and 10.2% of patients in these respective arms. Four TRAEs led to death, 3 in the serplulimab arm (pyrexia, acute coronary syndrome, and decreased platelet count) and 1 in the placebo arm (thrombocytopenia); all 4 deaths were immune related.

A head-to-head bridging trial is being conducted in the US comparing serplulimab with atezolizumab (Tecentriq), the current frontline standard of care for patients with ES-SCLC in the US.1 This trial is planned to support the FDA approval of serplulimab in the US.

References

1. Serplulimab approved in the EU for first-line treatment of extensive-stage small cell lung cancer (ES-SCLC). News release. Shanghai Henlius Biotech, Inc. February 5, 2025. Accessed February 5. 2025. https://www.prnewswire.com/news-releases/serplulimab-approved-in-the-eu-for-first-line-treatment-of-extensive-stage-small-cell-lung-cancer-es-sclc-302368903.html
2. Cheng Y, Han L, Wu L, et al. ASTRUM-005 study group. effect of first-line serplulimab vs placebo added to chemotherapy on survival in patients with extensive-stage small cell lung cancer: the ASTRUM-005 randomized clinical trial. JAMA. 2022;328(12):1223-1232. doi:10.1001/jama.2022.16464