A Phase 3 Study on Serplulimab Plus Chemo for First-Line ES-SCLC

Monoclonal antibodies targeting programmed death-ligand 1 (PD-L1) have been approved for the primary treatment of extensive-stage small-cell lung cancer (ES-SCLC) when used with chemotherapy. The efficacy of a programmed death 1 (PD-1) inhibitor in conferring comparable survival advantages to this particular group of patients is yet to be established. The present study evaluated the effectiveness and safety of serplulimab, a new humanized monoclonal anti-PD-1 antibody, in combination with chemotherapy for patients with previously untreated ES-SCLC. In this phase 3 trial (NCT04063163), which was international, randomized, double-blind, and multicenter, patients diagnosed with ES-SCLC without prior systemic therapy were randomly assigned (2:1) to receive intravenous serplulimab 4.5 mg/kg or placebo every 3 weeks. Intravenous carboplatin and etoposide were administered to all patients in 3-week intervals for a maximum of 4 cycles. The principal outcome measure was overall survival (OS). The secondary endpoints encompass progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety measures. During the period spanning from September 12, 2019, to April 27, 2021, a total of 585 patients were subjected to randomization (with 389 patients assigned to the serplulimab group and 196 patients assigned to the placebo group). Upon conducting an interim analysis, the observed median follow-up duration was 12.3 months.

The group administered with serplulimab exhibited a statistically significant increase in median overall survival as compared to the placebo group (15.4 vs. 10.9 months; hazard ratio [HR] 0.63, 95% CI 0.49–0.82; P < 0.001). The median progression-free survival (PFS) as evaluated by the independent radiology review committee (IRRC) according to the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 was notably extended in the serplulimab cohort compared to the placebo cohort (5.8 versus 4.3 months; hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.38–0.59; P< 0.001). Enhancements in efficacy were noted in ORR (80.2% versus 70.4%) and DoR (5.6 versus 3.2 months) as evaluated by IRRC in accordance with RECIST v1.1. Treatment-emergent adverse events (TEAEs) of grade ≥3, associated with serplulimab or placebo, were observed in 129 (33.2%) and 54 (27.6%) patients, respectively. The serplulimab group exhibited a higher incidence of immune-related treatment-emergent adverse events (TEAEs) than the placebo group (37% vs. 18.4%). The most significant contrast was observed in endocrine disorders (18.3% vs. 4.6%), frequently documented in anti-PD-1/PD-L1 therapies. Four fatalities were observed during the study, including one acute coronary syndrome, one pyrexia, and one decreased platelet count in the serplulimab group. Additionally, one case of thrombocytopenia was reported in the placebo group. These events are potentially associated with the study drugs. The administration of Serplulimab combined with chemotherapy as the primary treatment option demonstrated notable advantages and a tolerable safety profile in patients with extensive-stage small cell lung cancer (ES-SCLC) compared to chemotherapy alone. The global phase 3 study showcased the benefits of OS in previously untreated ES-SCLC patients through a PD-1 inhibitor.

Source:https://meetings.asco.org/abstracts-presentations/207324

Clinical Trail:https://clinicaltrials.gov/ct2/show/NCT04063163

Ying Cheng, Liang Han, Lin Wu, Jun Chen, Hongmei Sun, Guilan Wen, Yinghua Ji, Mikhail Dvorkin, Jianhua Shi, Zhijie Pan, Jinsheng Shi, Xicheng Wang, Yuansong Bai, Tamar Melkadze, Yueyin Pan, Xuhong Min, Maksym Viguro, Yan Xu, Qingyu Wang, Jun Zhu/Serplulimab, a novel anti-PD-1 antibody, plus chemotherapy versus chemotherapy alone as first-line treatment for extensive-stage small-cell lung cancer: An international randomized phase 3 study/J Clin Oncol 40, 2022 (suppl 16; abstr 8505) DOI10.1200/JCO.2022.40.16_suppl.8505