A phase 3 trial provides evidence of efficacy for serplulimab as first-line treatment in patients with extensive-stage small cell lung cancer. The programmed cell death ligand 1 inhibitor was compared with placebo in ASTRUM-005, an international, double-blind, randomized clinical trial of 585 patients, all of whom also received chemotherapy with carboplatin and etoposide.
Based on a primary outcome of overall survival and 13 secondary outcomes, the investigators found: “As of the data cutoff (October 22, 2021) for this interim analysis, the median duration of follow-up was 12.3 months (range, 0.2–24.8 months). The median overall survival was significantly longer in the serplulimab group (15.4 months [95% CI, 13.3 months–not evaluable]) than in the placebo group (10.9 months [95% CI, 10.0–14.3 months]) (hazard ratio, 0.63 [95% CI, 0.49–0.82]; P < .001). The median progression-free survival (assessed by an independent radiology review committee) also was longer in the serplulimab group (5.7 months [95% CI, 5.5–6.9 months]) than in the placebo group (4.3 months [95% CI, 4.2–4.5 months]) (hazard ratio, 0.48 [95% CI, 0.38–0.59]). Treatment-related adverse events that were grade 3 or higher occurred in 129 patients (33.2%) in the serplulimab group and in 54 patients (27.6%) in the placebo group.”
Editorial: “In their review of serplulimab for US approval, the FDA may possibly consider factors based on their prior evaluation of sintilimab earlier this year,” editorialists write. “Sintilimab, a PD-1 antibody, was combined with chemotherapy as initial treatment for patients with advanced non–small cell lung cancer in a trial conducted exclusively in China. Although the combination met its primary outcome of improving progression-free survival vs chemotherapy alone, a prior trial with pembrolizumab had already demonstrated the benefit of combination chemotherapy and immunotherapy in the same disease setting in 2018. In the case of sintilimab, the FDA determined that a trial conducted with a control intervention that was known to be inferior to US standards, and in a population not reflective of the US population, did not meet criteria for approval. Although the ASTRUM-005 trial was conducted in multiple countries and not just China, concerns about selection of the control intervention and generalizability may be similar to sintilimab in US regulatory review.”