A prospective clinical trial of camrelizumab in combination with chemoradiotherapy in patients with metastatic esophageal squamous cell carcinoma.

326 Background: Patients with metastatic esophageal squamous cell carcinoma (mESCC) have dismal prognosis, immune checkpoint inhibitors (ICIs) have been reported to offer objective response rate (ORR) of approximately 30% with a median progression-free survival (PFS) of 3.6 months for mESCC. Emerging evidence suggests that radiation might be a potent immunomodulator in multiple malignancies. In this trial, we aimed to assess the efficacy and safety of the combination of camrelizumab with radiotherapy and chemotherapy in mESCC. Methods: Patients with ECOG performance status of 0-1 and normal renal, liver and bone marrow function who initially diagnosed with mESCC or progressed after prior systemic treatments were received camrelizumab 200 mg of 21-day cycles plus radiotherapy (30-50Gy/10-25f) and platinum-based combination chemotherapy. The primary endpoint was disease control rate (DCR); secondary endpoints were PFS, overall survival (OS), objective response rate (ORR) and safety. Chinese Clinical Trial Registry identifier: ChiCTR2000040533. Results: From September 2018 to March 2021, 34 patients (85.3% men; median age, 60 years; 85.3% ECOG PS=1; 61.8% ≥2 organ metastases) were recruited. At a median follow-up of 14.3 months, the DCR was 70.6% (24 of 34; 95%CI, 52.3 to 84.3); ORR was 38.2% (13 of 34; 95%CI, 22.7 to 56.4); 44.1% had decrease in measurable disease; ≥6 months clinical benefit rate (CBR) was 41.2% (14 of 34; 95%CI, 25.1 to 59.2). Median PFS and OS of 9.5 months (95% CI, 7.1 to NR) and 19.5 months (95% CI, 13.9 to NR), respectively. Of the 34 patients, 32 (94.1%) had treatment-related adverse events (TRAEs) of any grade and 13 (38.3%) had grade 3-4 TRAEs that including reactive cutaneous capillary endothelial proliferation (17.6%), myelotoxicity (23.5%) and interstitial pneumonia (2.9%). No treatment-related death occurred. To the cut-off date of observation, 15 (44.1%) patients died and 12 (35.3%) are still receiving the treatment without events. Conclusions: The combination of camrelizumab with radiotherapy and chemotherapy has notable efficacy compared with historical controls in mESCC with manageable safety. This combination therapy strategy should be validated in a larger trial in the future. Variable N=34 Clinical trial information: ChiCTR2000040533. [Table: see text]