First-Line Serplulimab Receives Positive CHMP Opinion for ES-SCLC

The European Medicines Agency’s Committee for Medicinal Products for Human Use (CHMP) has issued a positive opinion recommending the approval of serplulimab (Hetronifly; Hansizhuang in China) for the first-line treatment of patients with extensive-stage small cell lung cancer (ES-SCLC).¹

The recommendation was supported by data from the phase 3 ASTRUM-005 trial (NCT04063163). Initial findings from an interim analysis published in JAMA in 2022 showed that at a median follow-up of 12.3 months (range, 0.2-24.8), patients treated with first-line serplulimab plus chemotherapy (n = 389) experienced a median overall survival (OS) of 15.4 months (95% CI, 13.3-not evaluable) compared with 10.9 months (95% CI, 10.0-14.3) for those given placebo plus chemotherapy (n = 196; HR, 0.63; 95% CI, 0.49-0.82; P < .001).² Additionally, the median progression-free survival (PFS) was 5.7 months (95% CI, 5.5-6.9) in the serplulimab arm vs 4.3 months (95% CI, 4.2-4.5) in the placebo arm (HR, 0.48; 95% CI, 0.38-0.59).

Updated data from the study presented at the 2024 ASCO Annual Meeting demonstrated that patients in the experimental arm achieved a median OS of 15.8 months (95% CI, 13.9-17.4) compared with 11.1 months (95% CI, 10.0-12.4) for those in the placebo arm (HR, 0.61; 95% CI, 0.50-0.74; P < .001).³

“The positive opinion from CHMP signifies a major milestone in our efforts to accelerate the global reach of our products, and further validates Henlius’ patient-centered [research and development] approach and commitment to global strategy,” Jason Zhu, MD, MBA, executive director and chief executive officer of Henlius Biotech, stated in a news release.¹ “We look forward to the formal approval of this treatment in Europe, bringing more treatment options and hope to patients there and worldwide.”

Serplulimab was previously approved in China and other countries in Southeast Asia for the first-line treatment of patients with ES-SCLC, based on prior data from ASTRUM-005.

The randomized, double-blind, phase 3 study enrolled patients at least 18 years of age with histologically or cytologically diagnosed ES-SCLC who had received no prior systemic therapy for their disease and had at least 1 measurable lesion as assessed by independent radiology review committee (IRRC) per RECIST 1.1 criteria. An ECOG performance status of 0 or 1 was also required.³

Patients were randomly assigned 2:1 to receive serplulimab at 4.5 mg/kg on day 1 plus carboplatin at area under the curve 5 on day 1 and etoposide at 100 mg/m² on days 1 to 3 of each 3-week cycle for up to 4 cycles; or placebo plus the same regimen of carboplatin and etoposide for up to 4 cycles. Patients then received serplulimab at 4.5 mg/kg or placebo once every 3 weeks until disease progression or unacceptable toxicity.

OS served as the trial’s primary end point. Secondary end points included PFS, time to second progression, overall response rate (ORR), duration of response (DOR), safety, pharmacokinetics, immunogenicity, biomarker explorations, and quality of life.

Additional updated data presented at the 2024 ASCO Annual Meeting showed that the median PFS per IRRC assessment was 5.8 months (95% CI, 5.6-6.9) in the serplulimab arm vs 4.3 months (95% CI, 4.2-4.4) in the placebo arm (HR, 0.46; 95% CI, 0.38-0.57).

The confirmed ORR by IRRC assessment was 68.9% (95% CI, 64.0%-73.5%) in the experimental arm vs 58.7% (95% CI, 51.4%-65.6%) in the control arm. All responders in the placebo arm experienced partial responses, whereas 1.5% of patients in the serplulimab arm had a complete response. The median DOR was 6.8 months (95% CI, 5.5-7.9) and 4.2 months (95% CI, 3.1-4.2) in the serplulimab and placebo arms, respectively.

Safety data published from the interim analysis in 2022 showed that treatment-emergent adverse effects (TEAEs) were reported in 95.6% of patients in the serplulimab group vs 97.4% of patients in the placebo group. The rates of grade 3 or higher TEAEs were 82.5% and 80.1%, respectively.²

The rates of any-grade treatment-related AEs (TRAEs) were 69.9% for the experimental arm vs 56.1% for the control arm. The respective rates of grade 3 or higher TRAEs were 33.2% and 27.6%. The most common grade 3 or higher TRAEs included decreased neutrophil count (serplulimab arm,14.1%; placebo arm, 13.8%), decreased white blood cell count (8.5%; 8.7%), decreased platelet count (6.2%; 8.2%), and anemia (5.4%; 5.6%).

References

1. Henlius receives positive CHMP opinion for HANSIZHUANG as first-line treatment for extensive-stage small cell lung cancer. News release. Henlius Biotech. September 20, 2024. Accessed September 23, 2024. https://www.henlius.com/en/NewsDetails-4712-26.html
2. Cheng Y, Han L, Wu L, et al. 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
3. Cheng Y, Han L, Wu L, et al. Serplulimab vs. placebo combined with chemotherapy as first-line treatment for extensive-stage small-cell lung cancer: extended follow-up results and patient-reported outcomes from the international phase 3 ASTRUM-005 study. J Clin Oncol. 2024;42(suppl 16):8100. doi:10.1200/JCO.2024.42.16_suppl.8100