Efficacy, Safety, and Correlative Biomarkers of Toripalimab in Previously Treated Recurrent or Metastatic Nasopharyngeal Carcinoma: A Phase II Clinical Trial (POLARIS-02)

• DOI: 10.1200/jco.20.02712
• Publication Date: 2021-01-25T21:00:56Z
• Authors: Feng-Hua Wang; Xiao-Li Wei; Jifeng Feng; Qi Li; Nong Xu; Xi-Chun Hu; Wangjun Liao; Yi Jiang; Xiao-Yan Lin; Qing-yuan Zhang; Xiang-Lin Yuan; Hai-Xin Huang; Ye Chen; Guang-Hai Dai; Jian-Hua Shi; Lin Shen; Shu-Jun Yang; Yong-Qian Shu; Yun-Peng Liu; Weifeng Wang; Hai Wu; Hui Feng; Sheng Yao; Rui-Hua Xu
• Keywords: Clinical endpoint; Progression-free survival; Refractory (planetary science)

As yet, no checkpoint inhibitor has been approved to treat nasopharyngeal carcinoma (NPC). This study was aimed evaluate the antitumor activity, safety, and biomarkers of toripalimab, a new programmed death-1 (PD-1) for recurrent or metastatic NPC (RM-NPC) refractory standard chemotherapy.In this single-arm, multicenter phase II study, patients with RM-NPC received 3 mg/kg toripalimab once every 2 weeks via intravenous infusion until confirmed disease progression unacceptable toxicity. The primary end point objective response rate (ORR). secondary points included duration (DOR), progression-free survival (PFS), overall (OS).Among all 190 patients, ORR 20.5% median DOR 12.8 months, PFS 1.9 OS 17.4 months. Among 92 who failed at least two lines systemic chemotherapy, 23.9%. ORRs were 27.1% 19.4% in PD-L1+ PD-L1- respectively (P = .31). Patients ≥ 50% decrease plasma Epstein-Barr virus (EBV) DNA copy number on day 28 had significantly better than those < decrease, 48.3% versus 5.7% .0001). Tumor mutational burden value 0.95 muts/mega-base cohort predictive response. Whole-exome sequencing results from 174 revealed that genomic amplification 11q13 region ETV6 alterations poor responses toripalimab.The POLARIS-02 demonstrated manageable safety profile durable clinical chemorefractory NPC. An early EBV correlated favorable