IMPORTANCE Standard first-line therapy for advanced or metastatic esophageal carcinoma is chemotherapy, but the prognosis remains poor. Camrelizumab (an anti-programmed death receptor 1 [PD-1] antibody) showed antitumor activity in previously treated advanced or metastatic esophageal squamous cell carcinoma.OBJECTIVE To evaluate the efficacy and adverse events of camrelizumab plus chemotherapy vs placebo plus chemotherapy as a first-line treatment in advanced or metastatic esophageal squamous cell carcinoma. DESIGN, SETTING, AND PARTICIPANTSThis randomized, double-blind, placebo-controlled, multicenter, phase 3 trial (ESCORT-1st study) enrolled patients from 60 hospitals in China between December 3, 2018, and May 12, 2020 (final follow-up, October 30, 2020. A total of 751 patients were screened and 596 eligible patients with untreated advanced or metastatic esophageal squamous cell carcinoma were randomized.INTERVENTIONS Patients were randomized 1:1 to receive either camrelizumab 200 mg (n = 298) or placebo (n = 298), combined with up to 6 cycles of paclitaxel (175 mg/m 2 ) and cisplatin (75 mg/m 2 ). All treatments were given intravenously every 3 weeks. MAIN OUTCOMES AND MEASURESCoprimary end points were overall survival (significance threshold, 1-sided P < .02) and progression-free survival (significance threshold, 1-sided P < .005). RESULTSOf the 596 patients randomized (median age, 62 years [interquartile range, 56-67 years]; 523 men [87.8%]), 1 patient in the placebo-chemotherapy group did not receive planned treatment. A total of 490 patients (82.2%) had discontinued the study treatment. The median follow-up was 10.8 months. The overall survival for the camrelizumabchemotherapy group was a median of 15.3 months (95% CI, 12.8-17.3; 135 deaths) vs a median of 12.0 months (95% CI, 11.0-13.3; 174 deaths) for the placebo-chemotherapy group (hazard ratio [HR] for death, 0.70 [95% CI, 0.56-0.88]; 1-sided P = .001). Progression-free survival for camrelizumab plus chemotherapy was a median of 6.9 months (95% CI, 5.8-7.4; 199 progression or deaths) vs 5.6 months (95% CI, 5.5-5.7; 229 progression or deaths) for the placebo-chemotherapy group (HR for progression or death, 0.56 [95% CI, 0.46-0.68]; 1-sided P < .001). Treatment-related adverse events of grade 3 or higher occurred in 189 patients (63.4%) in the camrelizumab-chemotherapy group and 201 (67.7%) in the placebo-chemotherapy group, including treatment-related deaths among 9 patients (3.0%) and 11 patients (3.7%), respectively.CONCLUSIONS AND RELEVANCE Among patients with advanced or metastatic esophageal squamous cell carcinoma, the addition of camrelizumab to chemotherapy, compared with placebo and chemotherapy, significantly improved overall survival and progression-free survival.

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ImportanceProgrammed cell death ligand 1 inhibitors combined with chemotherapy has changed the approach to first-line treatment in patients with extensive-stage small cell lung cancer (SCLC). It remained unknown whether adding a programmed cell death 1 (PD-1) inhibitor to chemotherapy provided similar or better benefits in patients with extensive-stage SCLC, which would add evidence on the efficacy of checkpoint inhibitors in the treatment of extensive-stage SCLC.ObjectiveTo evaluate the efficacy and adverse event profile of the PD-1 inhibitor serplulimab plus chemotherapy compared with placebo plus chemotherapy as first-line treatment in patients with extensive-stage SCLC.Design, Setting, and ParticipantsThis international, double-blind, phase 3 randomized clinical trial (ASTRUM-005) enrolled patients at 114 hospital sites in 6 countries between September 12, 2019, and April 27, 2021. Of 894 patients who were screened, 585 with extensive-stage SCLC who had not previously received systemic therapy were randomized. Patients were followed up through October 22, 2021.InterventionsPatients were randomized 2:1 to receive either 4.5 mg/kg of serplulimab (n = 389) or placebo (n = 196) intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 12 weeks.Main Outcomes and MeasuresThe primary outcome was overall survival (prespecified significance threshold at the interim analysis, 2-sided P &amp;lt; .012). There were 13 secondary outcomes, including progression-free survival and adverse events.ResultsAmong the 585 patients who were randomized (mean age, 61.1 [SD, 8.67] years; 104 [17.8%] women), 246 (42.1%) completed the trial and 465 (79.5%) discontinued study treatment. All patients received study treatment and were included in the primary analyses. 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 &amp;lt; .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.Conclusions and RelevanceAmong patients with previously untreated extensive-stage SCLC, serplulimab plus chemotherapy significantly improved overall survival compared with chemotherapy alone, supporting the use of serplulimab plus chemotherapy as the first-line treatment for this patient population.Trial RegistrationClinicalTrials.gov Identifier: NCT04063163

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8505 Background: Monoclonal antibodies against programmed death-ligand 1 (PD-L1) have been approved for the first-line treatment of extensive-stage small-cell lung cancer (ES-SCLC) in combination with chemotherapy. However, whether a programmed death 1 (PD-1) inhibitor provides similar survival benefit in this patient population remains unclear. In this study, the efficacy and safety of serplulimab, a novel humanized monoclonal anti-PD-1 antibody, were assessed in combination with chemotherapy in previously untreated ES-SCLC patients. Methods: In this international, randomized, double-blind, multicenter, phase 3 trial (NCT04063163), patients with ES-SCLC who had not received prior systemic therapy were randomized (2:1) to receive serplulimab 4.5 mg/kg or placebo intravenously every 3 weeks. All patients received intravenous carboplatin and etoposide every 3 weeks for up to 4 cycles. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), objective response rate (ORR), duration of response (DoR), and safety. Results: Between September 12, 2019 and April 27, 2021, 585 patients were randomized (serplulimab group, n = 389; placebo group, n = 196). At interim analysis, the median follow-up duration was 12.3 months. Median OS was significantly prolonged in the serplulimab group than the placebo group (15.4 vs.10.9 months; hazard ratio [HR] 0.63, 95% CI 0.49–0.82; P < 0.001). Median PFS assessed by the independent radiology review committee (IRRC) per RECIST v1.1 was significantly longer in the serplulimab group than the placebo group (5.8 vs. 4.3 months; HR 0.47, 95% CI 0.38–0.59; P < 0.001). Efficacy improvements were also observed in ORR (80.2% vs. 70.4%) and DoR (5.6 vs. 3.2 months) as assessed by IRRC per RECIST v1.1. Grade ≥3 treatment-emergent adverse events (TEAEs) related to serplulimab or placebo were reported in 129 (33.2%) and 54 (27.6%) patients in the respective groups. Incidence of immune-related TEAEs was higher in the serplulimab group compared to the placebo group (37% vs. 18.4%), with the largest difference in endocrine disorders (18.3% vs. 4.6%), which are commonly reported with anti-PD-1/PD-L1 therapies. Four deaths (1 acute coronary syndrome, 1 pyrexia, and 1 platelet count decreased in the serplulimab group; 1 thrombocytopenia in the placebo group) that might be related to study drugs were reported. Conclusions: Serplulimab plus chemotherapy as first-line treatment provided significant benefits and a manageable safety profile compared with chemotherapy alone in ES-SCLC patients. For the first time, OS benefits was demonstrated with a PD-1 inhibitor in a global phase 3 study among previously untreated ES-SCLC patients. Clinical trial information: NCT04063163.