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: Adult; Male; Pulmonary and Respiratory Medicine; China; Herpesvirus 4, Human; Cancer Research; Programmed Cell Death 1 Receptor; Advancements in Lung Cancer Research; Antibodies, Monoclonal, Humanized; Cancer Immunotherapy; 03 medical and health sciences; 0302 clinical medicine; Biochemistry, Genetics and Molecular Biology; Refractory (planetary science); Health Sciences; Nasopharyngeal carcinoma; Humans; Chemotherapy; Prospective Studies; Clinical endpoint; Immune Checkpoint Inhibitors; Internal medicine; Aged; Nasopharyngeal Carcinoma; Proto-Oncogene Proteins c-ets; Chromosomes, Human, Pair 11; Physics; Gastroenterology; Cohort; Life Sciences; Progression-free survival; Nasopharyngeal Neoplasms; Middle Aged; Astrobiology; Progression-Free Survival; Genomic Landscape of Cancer and Mutational Signatures; 3. Good health; Clinical trial; Radiation therapy; Oncology; Rapid Communications; Phases of clinical research; DNA, Viral; Disease Progression; Medicine; Biomarkers for Immunotherapy; Female; Surgery; Neoplasm Recurrence, Local

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