Camrelizumab plus with nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma: A single-arm, open-label phase II clinical trial.

e16005 Background: The poor prognosis of advanced esophageal cancer is worrisome, and the current first-line regimen with an effective rate is about 30%. Additionally, there is no standard second-line treatment after failure of first-line therapy. Programmed death receptor-1/programmed death ligand-1(PD-1/PD-L1) immune checkpoint inhibitors have achieved objective response rate (ORR) of 17-40%, following median overall survival (mOS) of 10.8 months in prior phase I-II clinical studies, but a large proportion of patients (pts) still failed to this response. And for CPS (combined positive score, CPS) < 1 pts, yet not have excellent treatment options. Previous study showed that nimotuzumab in combination with cisplatin and fluorouracil (PF) regimen reaching ORR of about 50%. So, we conducted the study. The primary endpoints were ORR, and the secondary endpoints included disease control rate (DCR), progression-free survival (PFS), duration of response (DoR), time to response (TTR), 9-month and 12-month survival rate, as well as safety. Methods: According to the relevant literature, the ORR of standard treatment is about 15%, and the efficacy of camrelizumab combined with nimotuzumab is expected to be 35%, alpha = 0.05. A total of 38 cases were enrolled in the two-stage Simon method, with a bilateral α value of 5% and a test efficiency of 90%. In the first phase, 23 pts were enrolled 15 pts in the second stage. If 9 or more pts reached response. The trial is considered successful. The dropout rate of 10% was calculated, and a total of 42 pts were enrolled. Results: In this phase II study, a total of 46 pts (full analysis set, FAS) were administered. The mean age was 65 years (range, 42-77). The ORR result was 32.6% (95%CI, 19.5%-48.0%, Clopper-Pearson method). The mOS was 12.68 months with median follow-up 19.88 months. The 9-month and 12-month survival rates were 73% and 58%, respectively. Median PFS was 9.40 months. The DCR was 83%(38/46), median DoR and TTR were not reached in FAS. For those pts without first-line immunotherapy, the ORR was 29.6% and the mOS was 10.94 months, and for first-line immunotherapy, the ORR was 36.8% and the mOS was 15.0 months. The CPS < 1 stratification factor result, ORR was 37.5%(3/8), and mOS was 14.3 months. In terms of safety, the incidence of treatment emergent adverse events (TEAEs) was 61% (28/46), of which 33% (15/46) had adverse events above grade 3 including 0 case related to nimotuzumab and 4 cases related to camrelizumab. The overall incidence of adverse drug reactions grade 3 or above was 9% (4/46), of which 0 case related to nimotuzumab and 4 case related to camralizumab. Conclusions: The combination of camrelizumab and nimotuzumab in the second-line treatment of advanced esophageal squamous cell carcinoma can improve ORR and prolong OS of pts with controllable toxicity.