Serplulimab 100mg/10ml solution for infusion vials

Abstract First-line systemic therapeutic options for advanced esophageal squamous cell carcinoma (ESCC) are limited. In this multicenter, double-blind phase 3 trial, a total of 551 patients with previously untreated, locally advanced or metastatic ESCC and PD-L1 combined positive score of ≥1 were randomized (2:1) to receive serplulimab (an anti-PD-1 antibody; 3 mg/kg) or placebo (on day 1), plus cisplatin (50 mg/m 2 ) (on day 1) and continuous infusion of 5-fluorouracil (1,200 mg/m 2 ) (on days 1 and 2), once every 2 weeks. The study met the primary endpoints. At the prespecified final analysis of progression-free survival (PFS) assessed by the blinded independent radiological review committee, serplulimab plus chemotherapy significantly improved PFS compared with placebo plus chemotherapy (median PFS of 5.8 months and 5.3 months, respectively; hazard ratio, 0.60; 95% confidence interval, 0.48–0.75; P < 0.0001). At the prespecified interim analysis of overall survival (OS), serplulimab plus chemotherapy also significantly prolonged OS compared with placebo plus chemotherapy (median OS of 15.3 months and 11.8 months, respectively; hazard ratio, 0.68; 95% confidence interval, 0.53–0.87; P = 0.0020). Grade 3 or higher treatment-related adverse events occurred in 201 (53%) and 81 (48%) patients in the serplulimab plus chemotherapy group and the placebo plus chemotherapy group, respectively. Serplulimab plus chemotherapy administered every 2 weeks significantly improved PFS and OS in patients with previously untreated, PD-L1-positive advanced ESCC, with a manageable safety profile. This study is registered with ClinicalTrials.gov ( NCT03958890 ).

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Background: The efficacy and safety of different immunosuppressants combined with chemotherapy in treating patients with small-cell lung cancer (extensive-disease small-cell lung cancer, limited-disease small-cell lung cancer and relapsed small-cell lung cancer) are still unknown, and there are no reports directly comparing the efficacy and safety of other immunotherapies. Objective: This study aimed to compare the efficacy and safety of first-line immunotherapy combined with chemotherapy in patients with small-cell lung cancer. Method: We searched Pubmed, Embase, Cochrane Library, CNKI, and Wanfang databases for relevant articles published from inception to November 11, 2020. The risk of bias of the included studies was conducted using the Cochrane risk-of-bias (RoB) tool. Multiple Bayesian network meta-analyses were performed. They conducted data analysis using R Studio and STATA version 15.1. The outcomes comprised overall survival (OS), progression-free survival (PFS), stability of response (SOR), duration of response (DOR) and adverse events of grade 3 or higher (AE grade≥3). A 95% confidence interval (CI) was provided for each estimate. Results: This meta-analysis included 16 RCT studies with 5898 patients. For OS, relative to chemotherapy (MD=-4.49; 95%CI [-7.97, -1.03]), durvalumab plus tremelimumab (MD=-4.62; 95%CI [-9.08, -0.11]), ipilimumab (MD=-4.26; 95%CI [-8.01, -0.3]) and nivolumab(MD=-5.66; 95%CI [-10.44, -1.11]) and nivolumab plus ipilimumab (MD=-4.56; 95%CI [-8.7, -0.1]), serplulimab can significantly increase the OS of SCLC patients. There was no significant difference between PFS, SOR and DOR. Analysis of AE showed that different immunotherapy combined chemotherapy regimens were similar to single chemotherapy regarding the overall incidence of AE grade≥3. However, after the cumulative ranking of the common symptoms of different adverse reactions, it was found that nivolumab ranked first in the occurrence probability of anemia (99.08%), fatigue (84.78%), and decreased appetite (89.66%). durvalumab was the most likely in nausea (75.4%). Pembrolizumab (76.24%) was most likely to cause pruritus. Chemotherapy combined with immunotherapy caused less diarrhea than chemotherapy alone (80.16%). Conclusions: According to our analysis, serplulimab combined with chemotherapy is more likely to show better efficacy with a manageable safety profile for small-cell lung cancer. However, the evidence for this comparison shows some limitations due to the number of literature. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023486053.

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Objective: The goal of this study was to investigate the effectiveness and safety of serplulimab in advanced solid tumors through a meta-analysis approach. Methods: An electronic search was conducted across the Embase, Web of Science, PubMed, and Cochrane Library databases, covering the period from each database's inception through 6 May 2025. Meta-analysis and related analyses, including subgroup, sensitivity, and publication bias assessments, were performed using Stata 16.0. The Cochrane Risk of Bias Assessment Tool (version 5.1.0) was utilized to measure the quality of randomized controlled trials (RCTs). For single-arm studies, quality was evaluated using the Methodological Index for Non-Randomized Studies (MINORS). Results: Ten studies, including three RCTs and seven single-arm studies, were analyzed, involving 2,020 patients. In the analysis of RCTs, serplulimab significantly elevated overall survival (OS) [HR = 0.68, 95% CI: 0.59-0.79, P < 0.01], disease control rate (DCR) [RR = 1.04, 95% CI: 1.01-1.08, P < 0.05], progression-free survival (PFS) [HR = 0.53, 95% CI: 0.47-0.61, P < 0.01], and objective response rate (ORR) [RR = 1.30, 95% CI: 1.09-1.56, P < 0.01]. The analysis of single-arm studies revealed that the ORR for serplulimab in solid tumors was [ES = 45%, 95% CI: 31%-59%, P < 0.01], and the DCR was [ES = 71%, 95% CI: 63%-80%, P < 0.01]. Among the ten studies, the most common adverse events included reductions in platelet count (0.32, 95% CI: 0.20-0.43), white blood cell count (0.30, 95% CI: 0.17-0.44), anemia (0.29, 95% CI: 0.09-0.48), and proteinuria (0.28, 95% CI: 0.17-0.38). Conclusion: Based on current research, serplulimab appears to be effective for solid tumors. However, given the limitations of the studies, for example, possible selection bias in single-arm studies, further multicenter, high-quality, large-sample RCTs are necessary to validate this conclusion.

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BACKGROUND: The ASTRUM-005 study previously demonstrated a significant overall survival (OS) benefit with serplulimab (a programmed death 1 inhibitor) plus chemotherapy versus chemotherapy alone in previously untreated extensive-stage small-cell lung cancer (ES-SCLC). Here, we report updated efficacy and safety results after an extended median follow-up of 19.8 months, along with the first report on findings from exploratory biomarker analyses. METHODS: A total of 585 patients were randomized in a 2:1 ratio to receive 4.5 mg/kg serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks, together with carboplatin and etoposide. The primary endpoint was OS. In addition, genomic profiling was performed to identify mutated genes, and quantitative serum proteome profiling was conducted to identify differentially expressed proteins (DEPs) between responders and non-responders of serplulimab plus chemotherapy. Regression analysis was subsequently used to construct a protein signature based on the DEPs. The associations between efficacy outcomes (objective response rate [ORR], OS, and progression-free survival [PFS]) and gene mutation status or DEP expression were also examined with regression analysis. Furthermore, the prognostic value of hematological parameters was evaluated. RESULTS: In the intent-to-treat population, the median OS was 15.8 months in the serplulimab group versus 11.1 months in the placebo group (hazard ratio, 0.62; 95% confidence interval, 0.50-0.76; P < 0.001). We identified 181 DEPs between responders and non-responders in the serplulimab group, from which a 15-protein signature was constructed. In the serplulimab group, patients with a higher 15-protein signature score were associated with significantly longer OS and PFS. Also, patients harboring tumor-suppressor retinoblastoma-1 (RB1) mutations or mutations in Notch pathway members showed improved ORR, OS, or PFS compared with their wild-type counterparts. Baseline neutrophil-to-lymphocyte ratio (NLR) and lactate dehydrogenase (LDH) level were independent prognosticators of patients with ES-SCLC. CONCLUSIONS: First-line serplulimab provided a sustained clinical benefit over placebo in patients with ES-SCLC. A 15-protein signature and mutations in RB1 or Notch pathway genes may serve as predictive biomarkers for benefits from serplulimab plus chemotherapy, while baseline NLR and LDH were independent prognosticators for ES-SCLC.

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Background: Serplulimab has shown promising results in the treatment of extensive-stage small cell lung cancer (ES-SCLC). This study aimed to evaluate the cost-effectiveness of serplulimab combination therapy compared to chemotherapy alone in patients with ES-SCLC from the Chinese healthcare system perspective. Methods: A partitioned survival model was developed to simulate the costs and outcomes of patients receiving serplulimab combination therapy or chemotherapy alone over a time horizon of 10 years. Data on overall survival, progression-free survival, and adverse events were obtained from the ASTRUM-005 randomized clinical trial. Costs were estimated from a healthcare system perspective and included drug acquisition, administration, monitoring, and management of adverse events. One-way and probabilistic sensitivity analyses were conducted to assess the impact of uncertainty on the results. Results: The base-case analysis showed that the combination of serplulimab and chemotherapy has demonstrated a significant increase in QALYs of 0.626 compared to chemotherapy alone. This improved outcome is accompanied by an additional cost of $10893.995. The ICER for incorporating serplulimab into the treatment regimen is $17402.548 per QALY gained. One-way sensitivity analysis confirmed the robustness of the findings. Probabilistic sensitivity analysis demonstrated that serplulimab combination therapy had a 97.40% high probability of being cost-effective compared to chemotherapy alone at the WTP thresholds. Conclusion: In contrast to chemotherapy as a standalone treatment, the addition of serplulimab to chemotherapy is believed to offer potential cost-effectiveness as a preferred initial therapeutic approach for patients with ES-SCLC in China.

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Immune checkpoint inhibitors (ICIs) have significantly improved survival outcomes in patients with advanced malignancies. However, their association with immune thrombocytopenia (ITP) poses a critical risk of severe hemorrhage and necessitates treatment discontinuation. The precise molecular mechanisms underlying ICI-associated ITP remain largely unclear, critically impeding the development of predictive biomarkers and targeted therapeutic strategies. Here, we present a case report of an elderly patient with stage IV gastric adenocarcinoma who developed recurrent ITP following programmed death receptor-1 (PD-1) inhibitor serplulimab, trastuzumab and chemotherapy. Notably, longitudinal peripheral blood mononuclear cell samples were collected and subjected to transcriptomic profiling before and after two distinct ITP episodes: the initial occurrence and a recurrence triggered by PD-1 inhibitor rechallenge, providing matched time-resolved data for mechanistic analysis. Our findings demonstrate that ICIs-induced ITP involves a dual pathogenic mechanism combining immune-mediated platelet destruction and intrinsic megakaryopoietic impairment providing a novel conceptual framework for understanding this immunotherapy complication. And this represents the first prospective longitudinal investigation combining serial biospecimen collection with transcriptomic profiling (RNA sequencing) to elucidate mechanisms underlying ICIs-induced ITP.

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