ESCORT-1st: A randomized, double-blind, placebo-controlled, phase 3 trial of camrelizumab plus chemotherapy versus chemotherapy in patients with untreated advanced or metastatic esophageal squamous cell carcinoma (ESCC).

Abstract

4000 Background: The current standard first-line therapy for advanced or metastatic ESCC is doublet chemotherapy, and prognosis remains poor. Camrelizumab, a humanized anti-PD-1 monoclonal antibody, has shown promising antitumor activity in previously treated advanced or metastatic ESCC (Huang et al. Lancet Oncol 2019). Immunotherapy may work synergistically with chemotherapy, but lacking clinical evidences in ESCC. Here, we report the findings of the phase 3 ESCORT-1st study which evaluated the efficacy and safety of camrelizumab plus chemotherapy vs chemotherapy in patients with untreated advanced or metastatic ESCC. Methods: Eligible patients were randomized 1:1 to receive camrelizumab 200 mg or placebo, both combined with up to 6 cycles of paclitaxel (175 mg/m2) and cisplatin (75 mg/m2). All were given intravenously Q3W. Tumor response was assessed every 6 weeks according to RECIST v1.1. Co-primary endpoints were OS and independent review committee (IRC)-assessed PFS. Efficacy was assessed in all randomized patients and safety was assessed in all treated patients. Data cutoff date for the prespecified interim OS and final PFS analysis was Oct 30, 2020. Results: From Dec 3, 2018 to May 12, 2020, 596 patients were randomized. 298 patients were treated with camrelizumb-chemotherapy and 297 patients with placebo-chemotherapy. With a median follow-up of 10.8 months, camrelizumab plus chemotherapy significantly improved OS compared with placebo plus chemotherapy (median, 15.3 month [95% CI 12.8-17.3] vs 12.0 months [11.0-13.3]; HR, 0.70 [95% CI, 0.56-0.88]; one-sided P = 0.0010). Camrelizumab plus chemotherapy was also superior for PFS (per IRC) vs placebo plus chemotherapy (median, 6.9 months [95% CI, 5.8-7.4] vs 5.6 months [95% CI, 5.5-5.7]; HR, 0.56 [95% CI, 0.46-0.68]; one-sided P < 0.0001). ORR per investigator was 72.1% in camrelizumab-chemotherapy group vs 62.1% in placebo-chemotherapy group, and median DoR was 7.0 vs 4.6 months. Incidences of grade ≥3 treatment-related AEs were comparable between the two groups (63.4% vs 67.7%), with decreased neutrophil count (39.9% vs 43.4%) as the most common one. Serious treatment-related AEs occurred in 30.2% vs 23.2% of patients, and treatment-related deaths occurred in 3.0% vs 3.7% of patients, respectively. Conclusions: Addition of camrelizumab to chemotherapy provided superior OS and PFS vs placebo plus chemotherapy, with a manageable safety profile. Camrelizumab in combination with paclitaxel and cisplatin has the potential to become a new standard first-line therapy in patients with advanced or metastatic ESCC. Based on this trial, we are submitting NDA to seek the approval from China National Medical Products Administration for camrelizumab plus chemotherapy in the treatment of untreated advanced or metastatic ESCC. Clinical trial information: NCT03691090.