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Objective: The aim of the current study was to evaluate the cost-effectiveness of serplulimab plus chemotherapy compared chemotherapy alone as first-line strategy for patients with ES-SCLC in China. Methods: A decision-analytic model that based on the Chinese health-care system perspective was conducted to evaluate the economic benefits for the two competing first-line treatment. The clinical survival and safety data were obtained from the ASTRUM-005 trial, cost and utility values were gathered from the local charges and previously published study. Both cost and utility values were discounted at an annual rate of 5%. Sensitivity analyses and subgroup analyses were performed to examine the robustness of the model results. Results: Serplulimab plus chemotherapy could bring additional 0.25 QALYs with the marginal cost of $37,569.32, resulting in an ICER of $147,908.74 per additional QALY gained. Sensitivity analyses confirmed that model results were robust. Subgroup analyses revealed that adding serplulimab to first-line chemotherapy were unlikely to be the cost-effective option for all subgroup patients. Conclusions: Serplulimab plus chemotherapy was unlikely to be the cost-effective first-line strategy compared with chemotherapy alone for patients with ES-SCLC in China. Reduced the price of serplulimab could increase its cost-effective. [ABSTRACT FROM AUTHOR]

Abstract Introduction This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma. Methods This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line). Group D was the only group in which participants received the study treatment in the first-line setting. The primary endpoint was safety. Results Following previous report on groups A and B, results of group D are herein presented. As of February 7, 2023, 61 patients were enrolled and were followed up for a median of 25.5 months. Grade ≥ 3 treatment-emergent adverse events were reported by 29 (47.5%) patients. One patient died from adverse events that were considered related to study treatment. Among the patients with at least one post-baseline tumor assessment (n = 58), the objective response rate was 29.3% (95% CI: 18.1–42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. IRRC-assessed median progression-free survival was 7.3 months (95% CI: 2.8–11.0), and median overall survival was 20.4 months (95% CI: 15.0–NE), respectively. Conclusion Serplulimab combination therapy with HLX04 showed a manageable safety profile as well as preliminary efficacy in patients with advanced HCC in the first-line setting.

Abstract Background The combination of anti‐PD‐1 antibody serplulimab and chemotherapy is considered standard first‐line therapy for advanced esophageal squamous cell carcinoma (ESCC), but few later‐line treatments are available. Here we evaluated the therapeutic efficacy of the recombinant, humanized anti‐EGFR antibody HLX07 when used alone or together with serplulimab and chemotherapy against advanced ESCC. Methods This open‐label, non‐randomized, two‐cohort, phase 2 trial involved patients 18‐75 years old with histologically or cytologically confirmed locally advanced, unresectable, or metastatic ESCC, and an Eastern Cooperative Oncology Group performance status of 0‐1. Patients who had failed first‐line immuno‐chemotherapy or at least two lines of other systemic therapy received HLX07 monotherapy intravenously at a dose of 1,000 mg once every 2 weeks (Q2W). Patients with no prior systemic therapy received HLX07 (1,000 mg, day 1) and serplulimab (200 mg, day 1) intravenously Q2W for up to 2 years, concurrently with cisplatin (50 mg/m2, day 1) for up to 8 cycles and 5‐fluorouracil (1,200 mg/m2, days 1‐2) for up to 12 cycles intravenously Q2W. The primary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results Overall, 50 patients were enrolled. In the HLX07 monotherapy group, ORR was 15.0% (3/20), and the median PFS was 1.5 months (95% confidence interval [CI], 1.3 to 3.7). The median duration of response was not reached, and the rate of patients showing an objective response lasting at least 6 months was 66.7% (95% CI, 5.4 to 94.5). Two (10.0%, 2/20) patients experienced grade 3‐4 treatment‐related adverse events (TRAEs), including hypomagnesemia, hypocalcemia, and fatigue. No patient experienced grade 5 TRAEs. In the HLX07 combination group, the ORR was 60.0% (18/30), and the median PFS was 7.8 months (95% CI, 3.3 to 9.1). Fourteen (46.7%, 14/30) patients experienced grade 3‐4 TRAEs, and one (3.3%, 1/30) patient died due to serplulimab‐related pneumonitis. Conclusions HLX07 monotherapy and its combination with serplulimab and chemotherapy showed manageable toxicity and promising antitumor activity in patients with recurrent or metastatic ESCC. Randomized controlled trials are warranted to further establish the safety and efficacy of HLX07 against ESCC. Trial registration This trial was registered at Clinicaltrials.gov (NCT05221658).

Introduction: This study aimed to evaluate the safety and preliminary efficacy of serplulimab, a novel programmed death-1 inhibitor, with or without bevacizumab biosimilar HLX04 as first-line treatment in patients with advanced hepatocellular carcinoma. Methods: This open-label, multicenter phase 2 study (clinicaltrials.gov identifier NCT03973112) was conducted in China and consisted of four treatment groups: group A (serplulimab 3 mg/kg plus HLX04 5 mg/kg, subsequent-line), group B (serplulimab 3 mg/kg plus HLX04 10 mg/kg, subsequent-line), group C (serplulimab 3 mg/kg, subsequent-line) and group D (serplulimab 3 mg/kg plus HLX04 10 mg/kg, first-line). Group D was the only group in which participants received the study treatment in the first-line setting. The primary endpoint was safety. Results: Following previous report on groups A and B, results of group D are herein presented. As of February 7, 2023, 61 patients were enrolled and were followed up for a median of 25.5 months. Grade ≥ 3 treatment-emergent adverse events were reported by 29 (47.5%) patients. One patient died from adverse events that were considered related to study treatment. Among the patients with at least one post-baseline tumor assessment (n = 58), the objective response rate was 29.3% (95% CI: 18.1–42.7) as assessed by an independent radiological review committee (IRRC) per RECIST v1.1. IRRC-assessed median progression-free survival was 7.3 months (95% CI: 2.8–11.0), and median overall survival was 20.4 months (95% CI: 15.0–NE), respectively. Conclusion: Serplulimab combination therapy with HLX04 showed a manageable safety profile as well as preliminary efficacy in patients with advanced HCC in the first-line setting. [ABSTRACT FROM AUTHOR]

Objective: In the ASTRUM-004 trial, serplulimab plus chemotherapy demonstrated significantly improved survival and controllable safety. This study assessed the cost-effectiveness of serplulimab plus chemotherapy in advanced squamous non‐small cell lung cancer (sqNSCLC), considering the perspective of the Chinese healthcare system. Methods: A decision tree and a Markov model were constructed to simulate the treatment. The interesting results included total cost, life-years (LYs), quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs). Scenario, one-way and probabilistic sensitivity analyses were used to examine model instability. Results: Compared with placebo plus chemotherapy, serplulimab plus chemotherapy had an ICER of $55,539.46/QALY ($47,278.84/LY). The ICERs were estimated to be $58,706.03/QALY, $48,978.34/QALY and $59,709.54/QALY inpatients with programmed death-ligand 1 expression level of tumor proportion score (TPS) < 1%, 1% ≤ TPS < 50%, and TPS ≥ 50%. The cost-effective prices of serplulimab were $168.276/100 mg, $349.157/100 mg, and $530.039/100 mg at the willingness-to-pay threshold of $12,574.30/QALY, $25,148.60/QALY, and $37,722.90/QALY. Patient weight and price of serplulimab created the most significant impact. Presently, the probability of serplulimab plus chemotherapy being cost-effective was 14.15%. Conclusion: Compared with placebo plus chemotherapy, serplulimab plus chemotherapy might not be cost-effective in the first-line treatment for advanced sqNSCLC. [ABSTRACT FROM AUTHOR]

With more than 20 anti-PD-1/PD-L1 antibodies currently marketed, anti-PD-1 therapy has become a cornerstone of tumor immunotherapy. These agents, however, exhibit notable disparities in their characteristics and clinical performance. For instance, in the field of small cell lung cancer (SCLC) where the majority of anti-PD-1 antibodies have yielded limited success, serplulimab produced impressive survival improvements and was approved for this indication by China’s National Medical Products Administration. Serplulimab’s marketing authorization application also received a positive opinion from the European Medicines Agency. Nevertheless, the molecular mechanism underpinning serplulimab’s superiority over its competitors remains elusive. We characterized the differences between serplulimab with approved PD-1/PD-L1 inhibitors (pembrolizumab and nivolumab) in terms of their binding features and functions in vitro and anti-tumor activity in vivo. Cellular pathways underlying the efficacy of serplulimab were also investigated. In comparison to competitors, serplulimab robustly induces PD-1 receptor endocytosis while fostering weaker PD-1-CD28 cis interactions. This phenomenon could mitigate the dephosphorylation of CD28 by SHP2, thereby facilitating sustained and robust T cell activation. While serplulimab and pembrolizumab exhibited similar performance in vitro and in vivo studies, serplulimab consistently demonstrated superior tumor killing efficacy compared to pembrolizumab upon co-administration with anti-TIGIT or anti-LAG3 inhibitors. Mechanistically, the serplulimab combination effectively reduces tumor microenvironment Treg cell populations, augments effector and memory T cell populations, and more potently modulates genes associated with diverse facets of the immune system, surpassing the effects of the pembrolizumab combination. In summary, our data underscore serplulimab as a differentiated PD-1 monoclonal antibody with best-in-class therapeutic potential.

Abstract Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS

Objective: To determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensivestage small cell lung cancer (ES-SCLC) in China. Methods: Using a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model. Results: In the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model. Conclusion: In China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective. [ABSTRACT FROM AUTHOR]

Patients with PD-L1-positive esophageal squamous-cell carcinoma (ESCC) were significantly more likely to survive when treated with serplulimab plus cisplatin plus 5-fluorouracil (serplulimab-CF). At this point, it is unknown whether this expensive therapy is cost-effective. From the Chinese healthcare system's perspective, we aimed to evaluate serplulimab-CF versus CF alone for cost-effectiveness. A partitioned survival model was constructed based on the ASTRUM-007 trial. Quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratio (ICER) were calculated. A further analysis of subgroups and scenarios was conducted. The willingness to pay (WTP) threshold of $38,258/QALY or $84,866/QALY is defined as three times the per capita gross domestic product value of the general region or affluent region. Compared with CF alone, in the overall (scenario 1), patients with PD-L1 expression level of 1 ≤ CPS < 10 (scenario 2), and patients with PD-L1 CPS ≥ 10 (scenario 3) populations, the ICERs were $69,025/QALY, $82,533/QALY, and $75,436/QALY for serplulimab-CF. Nevertheless, the probability of serplulimab-CF becoming cost-effective based on scenarios 1, 2, and 3 is only 2.71%, 0.94%, and 2.84%, respectively, at a WTP threshold of $38,258/QALY. When serplulimab costs < $4.84/mg, serplulimab-CF may be cost-effective at the WTP threshold of $38,258/QALY; otherwise, CF was preferred. Similar results were obtained from sensitivity analyses, suggesting the robustness of these findings. There was no cost-effectiveness in general regions of China for serplulimab-CF in PD-L1-positive ESCC compared to CF, although it is probably considered cost-effective in affluent regions. Serplulimab-CF may achieve favorable cost-effectiveness by lowering the price of serplulimab. [ABSTRACT FROM AUTHOR]

Objective: To explore the efficacy of serplulimab plus chemotherapy in esophageal squamous cell carcinoma (ESCC) patients with liver metastases. Methods: A post hoc exploratory analysis of ASTRUM‐007 study was performed, focusing on the association between the liver metastases status and the clinical outcomes. A systematic literature search of electronic databases was conducted to identify eligible randomized controlled trials for the meta‐analysis. Study‐level pooled analyses of hazard ratios (HRs) for PFS according to liver metastases were performed. Results: The post hoc analysis of ASTRUM‐007 showed that although patients with liver metastases had a worse prognosis comparing with the non‐liver metastases patients in both treatment arms (serplulimab plus chemotherapy arm: median PFS, 5.7 vs. 6.6 months, HR 1.57 [95% CI, 1.15–2.13]; median OS, 13.7 vs. 15.3 months, HR 1.48 [95% CI, 1.09–1.98]; placebo plus chemotherapy arm: median PFS, 4.3 vs. 5.5 months, HR 1.58 [95% CI, 1.01–2.39]; median OS, 10.3 vs. 11.2 months, HR 1.32 [95% CI, 0.84–2.00]), OS and PFS benefits derived from serplulimab plus chemotherapy versus placebo plus chemotherapy in this study were observed in both patients with liver metastases (HR of PFS: 0.60; 95% CI, 0.37–0.97; HR of OS: 0.68; 95% CI, 0.43–1.11) and the non‐liver metastases patients (HR of PFS: 0.62; 95% CI, 0.49–0.80; HR of OS: 0.69; 95% CI, 0.55–0.87) with similar magnitude. Three randomized controlled trials were included in the meta‐analysis. Pooled HRs demonstrated that the addition of anti‐PD‐1 antibodies significantly improved PFS compared to chemotherapy alone regardless of liver metastases status. Conclusions: This study reveals that the presence of liver metastases is a poor prognostic factor but does not affect the improvements in both PFS and OS brought by adding PD‐1 blockade to chemotherapy in ESCC patients. Predictive biomarkers for survival in these patients warrant further investigation. [ABSTRACT FROM AUTHOR]

Objective: To estimate the cost-effectiveness of adding serplulimab to chemotherapy for metastatic squamous non-small cell lung cancer (NSCLC) patients in a first-line setting from a Chinese perspective. Methods: A three-health state partitioned survival model was constructed to simulate disease development. The clinical data used in the model were derived from the ASTRUM-004 clinical trial. Only direct medical costs were included, and the utilities were derived from published literature. The quality-adjusted lifeyears (QALYs) and incremental cost-effectiveness ratio (ICER) were employed to evaluate health outcomes. Additionally, a sensitivity analysis was performed to verify the robustness of the results. Results: Compared with chemotherapy alone, the addition of serplulimab resulted in an increase of 0.63 QALYs with an incremental cost of $5,372.73, leading to an ICER of $8,528.14 per QALY. This ICER was significantly lower than 3 times China's per capita GDP. The one-way sensitivity analysis suggested that the utility of PFS was the most sensitive factor on ICERs, followed by the price of serplulimab. Conclusion: The combination of serplulimab and chemotherapy has been shown to be a cost-effective initial treatment option for patients with metastatic squamous NSCLC with the commonly accepted willingness-to-pay threshold of 3 times the GDP per capita per QALY in China. [ABSTRACT FROM AUTHOR]

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 combinedwith 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. [ABSTRACT FROM AUTHOR]

ObjectiveTo determine the cost-effectiveness of imported immune checkpoint inhibitors (ICIs) such as atezolizumab and durvalumab, and domestic ICIs like serplulimab and adebrelimab, in combination with chemotherapy for extensive-stage small cell lung cancer (ES-SCLC) in China.MethodsUsing a 21-day cycle length and a 20-year time horizon, a Markov model was established to compare the clinical and economic outcomes of five first-line ICIs plus chemotherapy versus chemotherapy alone, as well as against each other, from the perspective of the Chinese healthcare system. Transition probabilities were estimated by combining the results of the CAPSTONE-1 trial and a published network meta-analysis. Cost and health state utilities were collected from multiple sources. Both cost and effectiveness outcomes were discounted at a rate of 5% annually. The primary model output was incremental cost-effectiveness ratios (ICERs). A series of sensitivity analyses were preformed to assess the robustness of the model.ResultsIn the base-case analysis, the addition of first-line ICIs to chemotherapy resulted in the ICERs ranged from $80,425.31/QALY to $812,415.46/QALY, which exceeded the willing-to-pay threshold set for the model. When comparing these first-line immunochemotherapy strategies, serplulimab plus chemotherapy had the highest QALYs of 1.51286 and the second lowest costs of $60,519.52, making it is the most cost-effective strategy. Our subgroup-level analysis yielded results that are consistent with the base-case analysis. The sensitivity analysis results confirmed the validity and reliability of the model.ConclusionIn China, the combination of fist-line ICIs plus chemotherapy were not considered cost-effective when compared to chemotherapy alone. However, when these fist-line immunochemotherapy strategies were compared with each other, first-line serplulimab plus chemotherapy consistently demonstrated superiority in terms of cost-effectiveness. Reducing the cost of serplulimab per 4.5 mg/kg would be a realistic step towards making first-line serplulimab plus chemotherapy more accessible and cost-effective.

Chemotherapy combined with immunotherapy has significantly improved survival in patients with extensive-stage small cell lung cancer (ES-SCLC), and neoadjuvant immunotherapy combined with chemotherapy has emerged as the standard treatment for those with resectable non-small cell lung cancer (NSCLC). However, the potential benefits of surgery following neoadjuvant immunotherapy combined with chemotherapy in locally advanced SCLC remain unclear. Herein, we report a patient diagnosed with stage IIIB SCLC, who was administered five cycles of neoadjuvant serplulimab combined with chemotherapy followed by surgery, and subsequently achieved a pathologic complete response (pCR). Within a follow-up duration of six months, the patient displayed neither recurrence nor metastasis and experienced no treatmentrelated adverse reactions of any grade. Based on this case, for locally advanced SCLC, neoadjuvant serplulimab combined with chemotherapy followed by surgery may present an effective, safe, and potentially curative treatment strategy. Nonetheless, further prospective studies are needed to verify our findings. [ABSTRACT FROM AUTHOR]

Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. In total, 36 eligible participants experiencing SCLC transformation from EGFR -mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR -mutant NSCLC. • T-SCLC is a highly aggressive disease with a poor prognosis and lacks standard treatment. • Adding immunotherapy to chemotherapy might improve outcomes for T-SCLC but lacks clinical evidence. • The first prospective trial to investigate the efficacy of serplulimab plus chemotherapy for T-SCLC. • The exploratory analysis aims to identify potential biomarkers for immunotherapy in T-SCLC. [ABSTRACT FROM AUTHOR]

Background: This study evaluated the cost-effectiveness of serplulimab plus chemotherapy versus chemotherapy alone in treating advanced/metastatic esophageal squamous cell carcinoma (ESCC) within the Chinese health care system. Methods: A partitioned survival model based on ASTRUM-007 trial patient characteristics was developed. Efficacy, safety, and medical/economic data were obtained from the trial and real-world clinical practice. Costs, quality-adjusted life years (QALY), and incremental cost-effectiveness ratios (ICERs) were calculated for both treatment strategies. Sensitivity, subgroup, and scenario analyses were performed to assess the uncertainty impact. Results: Serplulimab combined with chemotherapy yielded an ICER of US$ 53,538.27/QALY. Deterministic sensitivity analysis identified patient survival and serplulimab price as influential parameters. Probabilistic sensitivity analysis showed a 47.33% probability of cost-effectiveness at a willingness-to-pay (WTP) threshold of US$ 53,541/QALY and 0.05% at three times China's GDP per capita. Subgroup analysis revealed that patients with a programmed death-ligand 1 (PD-L1) expression combined positive score (CPS) ⩾10 had a lower hazard ratio (0.59) and ICER (US$ 29,935.23/QALY), with a 95.36% probability of cost-effectiveness. Scenario analysis demonstrated that the drug donation discount policy significantly increased the likelihood of cost-effective serplulimab-chemotherapy combinations in Jiangsu, Fujian, and Guangdong at 99.99%, 99.90%, and 94.16%, respectively. Conclusion: Compared to chemotherapy alone, serplulimab combined with chemotherapy is currently not a cost-effective first-line treatment for advanced/metastatic ESCC in China. However, as serplulimab plus chemotherapy regimens evolve and price competition among programmed death 1 (PD-1) inhibitors intensifies, this combination may become a cost-effective treatment option. Plain language summary: Assessing Serplulimab's Value in Treating Advanced Esophageal Cancer in China In China, esophageal cancer patients often need chemotherapy due to late diagnosis. Serplulimab, an expensive new treatment, is not cost-effective when combined with chemotherapy for most patients. However, for specific patient groups with a PD-L1 expression CPS ⩾ 10, it is both effective and affordable. This finding helps health care leaders create better pricing strategies. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to evaluate the cost-effectiveness of the addition of serplulimab to chemotherapy (cisplatin and fluorouracil) for programmed deathligand 1 (PD-L1) positive advanced esophageal squamous cell carcinoma (ESCC) as the first-line treatment in China. Methods: A three-state Markov model was established to assess the incremental cost-effectiveness ratio (ICER) for serplulimab plus chemotherapy versus chemotherapy alone. Survival data were extrapolated from the ASTRUM-007 trial, cost data were derived from local sources, and utilities were derived from published literature. Health outcomes were measured as quality-adjusted lifeyears (QALYs). Sensitivity and probability sensitivity analyses were used to investigate the robustness of the model. Results: In the base-case analysis, compared with chemotherapy alone, serplulimab gained an additional 0.16 QALYs with an incremental cost of $29,547.88, leading to an ICER of $184,674.25/QALY. Additionally, the subgroup analyses presented that the ICERs of serplulimab plus chemotherapy were $157,892.50/QALY and $127,996.45/QALY in advanced ESCC patients with 1= CPS< 10 and CPS= 10, respectively. These ICERs significantly exceeded the Chinese willingness-to-pay (WTP) threshold. The deterministic sensitivity analysis illustrated that the cost of progression-free survival in serplulimab plus chemotherapy group was the parameterwith the strongest influence on the ICERs. Conclusion: In the Chinese health care system, with 3 times China's per capita gross domestic product as the WTP threshold, compared with chemotherapy alone, serplulimab combined chemotherapy is not economical for PD-L1-positive advanced ESCC in the first-line setting. [ABSTRACT FROM AUTHOR]

BackgroundSerplulimab 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.MethodsA 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.ResultsThe 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.ConclusionIn 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.

Objective: The ASTRUM-005 trial demonstrated that adding serplulimab to chemotherapy significantly prolonged the survival of patients with extensivestage small cell lung cancer (SCLC), but also increased the risk of adverse events. Given the high cost of serplulimab compared to chemotherapy, this study aimed to evaluate the cost-effectiveness of serplulimab plus chemotherapy as a firstline treatment for extensive-stage SCLC from the perspective of China’s healthcare system. Methods: A Markov model was developed to simulate the disease process of extensive-stage SCLC and estimate the health outcomes and direct medical costs of patients. Scenario analyses, univariate sensitivity analyses, and probabilistic sensitivity analyses were conducted to explore the impact of different parameters on model uncertainty. The primary model outcomes included costs, life-years (LYs), quality-adjusted life-years (QALYs), and the incremental cost-effectiveness ratio (ICER). Results: Compared to placebo plus chemotherapy, serplulimab plus chemotherapy resulted in an additional 0.25 life-years and 0.15 QALYs, but also increased costs by $26,402, resulting in an ICER of 179,161 USD/QALY. Sensitivity analysis showed that the ICER was most sensitive to the cost of serplulimab, and the probability that serplulimab was cost-effective when added to chemotherapy was only 0 at the willingness-to-pay threshold of 37,423 USD/ QALY. Scenario analysis revealed that price discounts on serplulimab could increase its probability of being cost-effective. Conclusion: Serplulimab plus chemotherapy is not a cost-effective strategy for first-line treatment of extensive-stage SCLC in China. Price discounts on serplulimab can enhance its cost-effectiveness. [ABSTRACT FROM AUTHOR]

Objective: The ASTRUM-007 trial (NCT03958890) demonstrated that serplulimab plus chemotherapy administered every 2-week significantly improved progression-free and overall survival in patients with previously untreated, programmed death-ligand 1 (PD-L1) positive advanced esophageal squamous-cell carcinoma (ESCC). This study was aimed to investigate the costeffectiveness of serplulimab plus chemotherapy in the first-line treatment of PDL1-positive advanced ESCC. Methods: A partitioned survival model with a 2-week cycle and a 10-year time horizon was constructed from the Chinese healthcare system perspective. The survival data, direct medical costs and utilities were derived from the ASTRUM-007 trial, YAOZHI database and published sources. Total costs, quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. Scenario, one-way and probabilistic sensitivity analyses were performed to assess the uncertainty around model parameters. Results: Compared with chemotherapy, serplulimab plus chemotherapy provided additional 0.27 QALYs with an incremental cost of $33,460.86, which had an ICER of $124,483.07 per QALY. The subgroup analyses revealed that the ICERs of serplulimab plus chemotherapy were $134,637.42 and $105,589.71 in advanced ESCC patients with 1 = CPS < 10 and CPS = 10, respectively. The price of serplulimab, patient weight, utility values and discount rate were the most influential parameters on base-case results. At a willingness-to-pay threshold of three times per capita GDP ($40,587.59) in 2022, the probability of serplulimab plus chemotherapy being cost-effective was 0% compared with chemotherapy. When the price of serplulimab decreased by 70%, the probabilities of serplulimab plus chemotherapy being cost-effective were 81.42%, 67.74% and 96.75% in advanced ESCC patients with PD-L1-positive, PD-L1 1=CPS<10 and CPS=10, respectively. Conclusion: Serplulimab plus chemotherapy in the first-line treatment for PD-L1-positive advanced ESCC might not be cost-effective in China. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate the cost-effectiveness of serplulimab versus regorafenib in previously treated unresectable or metastatic microsatellite instability-high (MSI-H)/deficient mismatch repair (dMMR) colorectal cancer in China. Methods: From the perspective of China's health-care system, a Markov model with three health states (progression free, progression, death) was developed for estimating the costs and health outcomes of serplulimab and regorafenib. Data for unanchored matching-adjusted indirect comparison (MAIC), standard parametric survival analysis, the mixed cure model, and transition probabilities calculation were obtained from clinical trials (ASTRUM-010 and CONCUR). Health-care resource utilization and costs were derived from governmentpublished data and expert interviews. Utilities used to calculate qualityadjusted life years (QALYs) were obtained from clinical trials and literature reviews. The primary outcome was the incremental cost-effectiveness ratio (ICER) expressed as cost/QALY gained. Four scenarios were considered in scenario analysis: (a) using original survival data without conducting MAIC; (b) limiting the time horizon to the follow-up time of the clinical trial of serplulimab; (c) adopting a fourfold increase in the risk of death; and (d) applying utilities from two other sources. One-way sensitivity analysis and probabilistic sensitivity analysis were also performed to assess the uncertainty of the results. Results: In the base-case analysis, serplulimab provided 6.00 QALYs at a cost of $68,722, whereas regorafenib provided 0.69 QALYs at a cost of $40,106. Compared with that for treatment with regorafenib, the ICER for treatment with serplulimab was $5,386/QALY, which was significantly lower than the triple GDP per capita of China in 2021 ($30,036), which was the threshold used to define the cost-effectiveness. In the scenario analysis, the ICERs were $6,369/QALY, $20,613/QALY, $6,037/QALY, $4,783/QALY, and $6,167/QALY, respectively. In the probabilistic sensitivity analysis, the probability of serplulimab being cost-effective was 100% at the threshold of $30,036/QALY. Conclusion: Compared with regorafenib, serplulimab is a cost-effective treatment for patients with previously treated unresectable or metastatic MSI-H/dMMR colorectal cancer in China. [ABSTRACT FROM AUTHOR]

Objective: We report the efficacy and safety of serplulimab, a novel humanized anti-programmed death-1 antibody, plus nanoparticle albumin-bound (nab)- paclitaxel in previously treated patients with programmed death ligand-1 (PDL1)-positive advanced cervical cancer. Methods: Patients diagnosed with PD-L1-positive (combined positive score ≥1) cervical cancer were enrolled in this single-arm, open-label, phase II study. They were given serplulimab 4.5 mg/kg for up to 2 years (35 dosing cycles) plus nabpaclitaxel 260 mg/m2 for up to six cycles once every 3 weeks. Primary endpoints were safety and objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST version 1.1. Secondary endpoints included ORR assessed by the investigator, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). Results: Between December 2019 and June 2020, 52 patients were screened and 21 were enrolled. IRRC-assessed ORR was 57.1% (95% confidence interval [CI] 34.0-78.2%); 3 (14.3%) patients achieved complete response and 9 (42.9%) partial response. The median DOR was not reached (NR) (95% CI 4.1-NR). IRRC-assessed median PFS was 5.7 months (95% CI 3.0-NR), and median OS was 15.5 months (95% CI 10.5-NR). Investigator-assessed ORR was 47.6% (95% CI 25.7-70.2%). Seventeen (81.0%) patients experienced grade ≥3 treatmentemergent adverse events. Grade =3 adverse drug reactions were reported in 7 (33.3%) patients. Immune-related adverse events occurred in 12 (57.1%) patients. Conclusions: In previously treated patients with PD-L1-positive advanced cervical cancer, serplulimab plus nab-paclitaxel provided durable clinical activity and a manageable safety profile. [ABSTRACT FROM AUTHOR]

BackgroundFor patients with extensive-stage small cell lung cancer (ES-SCLC), serplulimab plus chemotherapy is beneficial as the first-line treatment. It is uncertain whether serplulimab plus chemotherapy will be more cost-effective. The aim of this study was to evaluate from the perspective of the Chinese healthcare system to assess the cost-effectiveness of serplulimab plus chemotherapy for patients with ES-SCLC.Materials and methodsThis study employed a partitioned survival model. Patients in the model were selected from ASTRUM-005 for their clinical characteristics and outcomes. In order to assess the robustness of the model, we conducted deterministic one-way sensitivity analyzes as well as probabilistic sensitivity analyzes. Subgroup analyzes were also conducted. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratio (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were analyzed.ResultsBased on the base-case analysis, serplulimab plus chemotherapy contributed to an increase in 0.826 life-years and 0.436 QALYs; an incremental cost of $52,331, yielded ICER of $120,149/QALY. Based on the willingness to pay (WTP) threshold of $37,669/QALY and $86,569/QALY, the INHB was −0.954 QALYs and − 0.169 QALYs and the INMB was -$35,924 and -$14,626, respectively. Based on the probabilistic sensitivity analysis results, serplulimab plus chemotherapy was unlikely to be cost-effective at a WTP threshold of $37,669/QALY and $86,569/QALY. One-way sensitivity analysis indicated that cost of serplulimab and body weight had the greatest impact on the model. Serplulimab plus chemotherapy could be cost-effective at a WTP threshold of $86,569/QALY when the cost of serplulimab was less than $5.24/mg or when the weight of the patient was less than 40.96 kg. Regardless of the WTP threshold at $37,669/QALY or $86,569. Serplulimab plus chemotherapy was not cost-effective in all subgroups.ConclusionSerplulimab plus chemotherapy was not cost-effective, despite having a prior clinical benefical and a relative safety profile compared with chemotherapy. With the reduction in the price of serplulimab, ES-SCLC patients treated with serplulimab plus chemotherapy may be able to achieve a favorable cost-effectiveness rate.

The efficacy and safety of first-line immune checkpoint inhibitors plus chemotherapy in the treatment of patients with extensive-stage small cell lung cancer (ES-SCLC) remains unevaluated, and there are no reports to directly compare the efficacy and safety among different immunotherapy (especially adebrelimab and surplulimab). Suitable phase III randomized controlled trials with two or more different arms were included. Independent reviewers screened and extracted relevant data and disagreements were resolved through consensus. Fixed-effect consistency models were used to calculate the overall survival (OS), progression-free survival (PFS), objective response rate, adverse events ≥ 3, and safety outcomes in the clinically relevant subgroups. In this network meta -analysis, six randomized controlled clinical trials (CAPSTONE-1, ASTRUM-005, CASPIAN, IMpower133, KEYNOTE-604, and an ipilimumab + chemotherapy trial) with totaling 3662 patients were involved. Compared to chemotherapy, immune checkpoint inhibitors plus chemotherapy present higher possibilities to bring about better OS and PFS. Serplulimab + chemotherapy significantly showed a better survival profit in comparison with ipilimumab + chemotherapy (0.67; 0.50–0.90). Compared with chemotherapy, adebrelimab + chemotherapy (0.72; 0,58–0.90), atezolizumab + chemotherapy (0.76; 0.60–0.96) durvalumab + chemotherapy (0.75; 0.62–0.91), and serplulimab + chemotherapy (0.63;0.49–0.82) all presented significantly better overall survival. In terms of progression-free survival, serplulimab + chemotherapy showed better efficacy in comparison with adebrelimab + chemotherapy (0.72; 0,53–0.97), atezolizumab + chemotherapy (0.62; 0.46–0.84), durvalumab + chemotherapy (0.60; 0.45–0.80). Compared with chemotherapy, adebrelimab + chemotherapy (0.67; 0.54–0.83) and serplulimab + chemotherapy (0.48; 0.48–0.86) all presented significantly better PFS. Immunotherapy plus chemotherapy had similar probabilities to cause adverse events of grade ≥ 3. In comparison with chemotherapy, immune checkpoint inhibitors plus chemotherapy were likely to be more suitable for the first-line treatment of ES-SCLC. According to our analysis, serplulimab plus chemotherapy and adebrelimab plus chemotherapy present higher possibilities to show better efficacy and safety, however, the level of evidence of this type of comparison is limited. [ABSTRACT FROM AUTHOR]

Introduction: The ASTRUM-005 trial (NCT04063163) revealed that combination serplulimab plus chemotherapy (etoposide and carboplatin [EC]) treatment was associated with survival advantages relative to chemotherapy alone in patients diagnosed with extensive-stage small-cell lung cancer (ES-SCLC). As these immunochemotherapeutic regimens are extremely expensive, however, it is critical that the relative cost-effectiveness of combination serplulimab and chemotherapy treatment as a first-line treatment for ES-SCLC patients be examined in detail. Methods: The cost-effectiveness of combined serplulimab plus chemotherapeutic treatment was examined using a comprehensive Markov model with a 10-year boundary, enabling the calculation of overall cost, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER).Model instability was interrogated through one-way and probabilistic sensitivity analyses. Results: Serplulimab plus chemotherapy or chemotherapy alone respectively yielded 1.217 QALYs (2.243 LYs) and 0.885 QALYs (1.661 LYs) with corresponding total costs of $11,202 and $7,194, with an ICER of $12,077 per QALY($6,883 per LY). This model was most strongly influenced by the utility of progression-free survival. Probabilistic sensitivity analysis showed that serplulimab plus chemotherapy had a 91.6% probability of being cost-effective at a willingness-to-pay (WTP) of $37,653 per QALY (3 × capita gross domestic product of China in 2021). In subgroup analyses, this combination treatment regimen was found to be most cost-effective in patients who were former smokers, had an ECOG performance status of 0, and were diagnosed with brain metastases. Conclusion: From a payer perspective in China, combination serplulimab plus chemotherapy treatment represents a cost-effective first-line intervention for ES-SCLC patients. [ABSTRACT FROM AUTHOR]

Introduction: Lung cancer remains the most common malignancy and the leading cancer-related death among the elderly in China, which deserves more research attention. Immunotherapy combined with platinum-based doublet chemotherapy has been approved as the standard treatment for advanced non-small cell lung cancer (NSCLC) patients who are devoid of specific gene mutations or fusions. Given that patients with NSCLC over the age of 65 typically exhibit declining organ function and physical condition, they often showed reduced tolerance for this rigorous treatment regimen. However, the KEYNOTE-042 study illuminated a promising pathway: in patients testing positive for programmed death-ligand 1 (PD-L1), immunotherapy alone has demonstrated a superior overall survival (OS) compared to platinum-based doublet chemotherapy. This suggests that moderating the intensity of chemotherapy and prioritizing immunotherapy may be a gentler alternative in elderly demographic., Patients and Methods: This multicenter phase II clinical trial named UNICORN aimed to enroll 49 patients aged 65 and older, utilizing paclitaxel or nab-paclitaxel for those with squamous NSCLC, and pemetrexed for those diagnosed with lung adenocarcinoma. The treatment protocol entails 4 cycles of serplulimab plus chemotherapy followed by an extended regimen of serplulimab maintenance, spanning a total of 35 cycles. Primary endpoints of this study are progression-free survival (PFS), disease control rate (DCR) and the secondary endpoints are OS, objective control rate (ORR) and safety metrics., Conclusion: This is the first study to evaluate the efficacy and safety of serplulimab combined with either paclitaxel or pemetrexed in elderly treatment-naïve patients with stage IV NSCLC whose PD-L1 are positive., Competing Interests: Disclosure All authors declare that conflicts of interest do not exist., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Whether or not the addition of immunotherapy to current standard-of-care treatments can improve efficacy in proficient mismatch repair (pMMR)/microsatellite-stable (MSS) metastatic colorectal cancer (mCRC), the predominant type of mCRC, is unclear., Methods: This randomized, double-blind, phase 2 part of a phase 2/3 trial was conducted at 23 hospitals across China (ClinicalTrials.gov: NCT04547166). Patients with unresectable metastatic/recurrent colorectal adenocarcinoma and no prior systemic therapy were randomly assigned 1:1 to receive every-3-weeks intravenous serplulimab (300 mg) plus HLX04 (7.5 mg/kg) and XELOX (serplulimab group) or placebo (300 mg) plus bevacizumab (7.5 mg/kg) and XELOX (placebo group). The primary endpoint was independent radiology review committee (IRRC)-assessed progression-free survival (PFS). Secondary endpoints included other efficacy endpoints and safety., Findings: Between July 16, 2021, and January 20, 2022, 114 patients were enrolled and randomly assigned to the serplulimab (n = 57) or placebo (n = 57) group. All patients had stage IV CRC, and 95.7% of the patients with available microsatellite instability (MSI) status were MSS. With a median follow-up duration of 17.7 months, median PFS was prolonged in the serplulimab group (17.2 vs. 10.7 months; hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.31-1.14). Although the median overall survival (OS) was not reached for either group, a trend of an OS benefit was observed for the serplulimab group (HR, 0.77; 95% CI, 0.41-1.45). 36 (65.5%) and 32 (56.1%) patients in the serplulimab and placebo groups had grade ≥3 treatment-related adverse events, respectively., Conclusions: Serplulimab plus HLX04 and XELOX exhibits promising efficacy and is safe and tolerable in patients with treatment-naive mCRC., Funding: This work was funded by Shanghai Henlius Biotech, Inc., Competing Interests: Declaration of interests Y.K., H.Y., J.L., Q.W., and J. Zhu are employees of Shanghai Henlius Biotech, Inc. R.-H.X. reported participating on advisory boards for Astellas, MSD, AstraZeneca, Hengrui, BeiGene, Innovent, Hutchison, Junshi, Qilu, CPPC, and Keymed., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Combining immunotherapy with chemotherapy can provide improved survival in advanced squamous non-small-cell lung cancer (NSCLC) patients without targetable gene alterations. 537 previously untreated patients with stage IIIB/IIIC or IV squamous NSCLC without targetable gene alterations were enrolled and randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo, both in combination with nab-paclitaxel and carboplatin, intravenously in 3-week cycles. The primary endpoint of progression-free survival (PFS) was met at the first interim analysis. At the second interim analysis, PFS benefit was maintained in serplulimab-chemotherapy group (hazard ratio [HR] 0.53, 95% confidence interval [CI] 0.42–0.67). At the final analysis, serplulimab-chemotherapy significantly improved median OS compared to placebo-chemotherapy (HR 0.73, 95% CI 0.58–0.93; p = 0.010). Grade ≥3 serplulimab or placebo-related adverse events occurred in 126 (35.2%) and 58 (32.4%) patients, respectively. Our results demonstrate that adding serplulimab to chemotherapy significantly improves survival in advanced squamous NSCLC patients, with manageable safety. [Display omitted] • First-line serplulimab plus chemotherapy improves PFS and OS • This combination shows a manageable safety profile in advanced squamous NSCLC • Serplulimab plus chemotherapy represents another treatment option for these patients Zhou et al. demonstrate the efficacy and safety of serplulimab plus chemotherapy (nab-paclitaxel and carboplatin) in first-line patients with advanced squamous non-small-cell lung cancer. Compared with placebo plus chemotherapy, serplulimab plus chemotherapy prolongs progression-free survival and overall survival, with a manageable safety profile. [ABSTRACT FROM AUTHOR]

Small-cell lung cancer (SCLC) is an aggressive form of lung cancer with limited treatment options, especially for extensive-stage (ES) patients. We present a case of a 70-year-old male with ES-SCLC and asymptomatic brain metastasis who opted for immune monotherapy with serplulimab (an anti-PD-1 antibody). After four cycles, the patient achieved a confirmed partial response and a progression-free survival of over 1 year. Moreover, we observed a consistent decline in tumor biomarkers, and brain MRI indicated reduced metastatic activity. Remarkably, the patient tolerated the treatment well, with only mild diarrhea. This case highlights serplulimab's potential as a first-line treatment in select ES-SCLC patients, emphasizing the importance of further research on immunotherapy predictive biomarkers.

Introduction: Current treatments for patients with previously treated advanced hepatocellular carcinoma (HCC) provide modest survival benefits. We evaluated the safety and antitumor activity of serplulimab, an anti-PD-1 antibody, plus the bevacizumab biosimilar HLX04 in this patient population., Methods: In this open-label, multicenter, phase 2 study in China, patients with advanced HCC who failed prior systemic therapy received serplulimab 3 mg/kg plus HLX04 5 mg/kg (group A) or 10 mg/kg (group B) intravenously every 2 weeks. The primary endpoint was safety., Results: As of April 8, 2021, 20 and 21 patients were enrolled into groups A and B, and they had received a median of 7 and 11 treatment cycles, respectively. Grade ≥3 treatment-emergent adverse events were reported by 14 (70.0%) patients in group A and 12 (57.1%) in group B. Most immune-related adverse events were grade ≤3. The objective response rate was 30.0% (95% confidence interval [CI], 11.9-54.3) in group A and 14.3% (95% CI, 3.0-36.3) in group B. Median duration of response was not reached (95% CI, 3.3-not evaluable [NE]) in group A and was 9.0 months (95% CI, 7.9-NE) in group B. Median progression-free survival was 2.2 months (95% CI, 1.4-5.5) and 4.1 months (95% CI, 1.5-NE), and median overall survival was 11.6 months (95% CI, 6.4-NE) and 14.3 months (95% CI, 8.2-NE) in groups A and B, respectively., Conclusion: Serplulimab plus HLX04 showed a manageable safety profile and promising antitumor activity in patients with previously treated advanced HCC., Competing Interests: Xiaoli Hou, Qingyu Wang, and Jun Zhu are employees of Shanghai Henlius Biotech, Inc. Dr. Jia Fan is an associate editor of Liver Cancer. All other authors declare no potential conflicts of interest., (Copyright © 2022 by The Author(s). Published by S. Karger AG, Basel.)