Nimotuzumab plus concurrent chemoradiotherapy for locally advanced cervical squamous cell carcinoma: The randomized, phase 3 CC3 study.

5514 Background: Cervical cancer is the fourth common malignancy in women, with a 5-year overall survival rate of 24%-76.1%. At present, there are few studies on targeted drugs combined with concurrent chemoradiotherapy (CCRT) for locally advanced cervical cancer (LACC) and the survival results were not satisfactory. This CC3 study is the first randomized, controlled, multicenter phase 3 trial of EGFR combined with CCRT for advanced cervical cancer, aims to evaluate the efficacy and safety of nimotuzumab (humanized EGFR) in combination with CCRT for LACC. (NCT04678791). Methods: All patients with locally advanced cervical squamous cell carcinoma were randomized (1:1) to receive nimotuzumab (400mg, iv, weekly, for 6 weeks) combined with CCRT (cisplatin: 40 mg/m 2 , weekly, for 6 weeks; IMRT/VMAT: 45-50.4 Gy/25-28f; high-dose rate brachytherapy: 30-40 Gy, in 8 weeks) or CCRT alone. The primary endpoint was 3-year progression free survival (PFS) per RECIST 1.1. The secondary endpoints were 3-year overall survival (OS), objective response rate (ORR), complete response (CR) rate per RECIST v1.1, and safety per CTCAE v5.0. Results: Totally 286 patients were enrolled. 142 patients in the Nimo group (nimotuzumab combined with CCRT) and 144 in the CCRT group (CCRT alone). The baseline characteristics were balanced between the two groups. The 1-year PFS rate of the Nimo group was longer than that of CCRT group (96.1% vs. 92.1%, P=0.506). There was no significant difference in the risk ratio between the two groups (HR=0.76, 95% CI: 0.33-1.72, P=0.507), the 3-year PFS and 3-year OS were not reached. A total of 62 (43.99%) patients achieved partial response (PR) and 57 (40.14%) achieved CR in the Nimo group, 50 (34.72%) and 57 (39.58%) in the CCRT group, respectively. The ORR was 83.80% vs. 74.31% (P=0.049). The most common AEs were graded 1-2 as reported before. Follow-up is ongoing. Conclusions: Nimotuzumab combined with CCRT showed significant ORR improvement, longer trend in PFS and good safety in the treatment of LACC patients. Clinical trial information: NCT04678791 . [Table: see text]