Study design and participants
tumor, bleeding, cancer, Tumors, necrosis, autoimmune disease, Cancer
TUMOR, BLEEDING, LIVER METASTASES, CANCER, METASTATIC DISEASE, TUMORS, NECROSIS, ONCOLOGY, EVENTS, AUTOIMMUNE DISEASE, CANCER
This single­arm, open­label, phase 2 trial was done at a single cancer center in Guangzhou, China. The same inclusion criteria would be applied to both cohorts, but the patient selection criteria differed: cohort 1 included patients with platinum-resistant RM-NPC without received immune checkpoint inhibitors for recurrent or metastatic disease; cohort 2 included patients with immune checkpoint inhibitors-resistant RM-NPC. The first and last patients were officially enrolled in cohort 1 on 8 September 2020, and 30 August 2021, respectively. In cohort 2, patients were enrolled beginning on 2 November 2020, and ending on 7 September 2021.Eligible patients were aged 18–75 years with an Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, histologically or cytologically confirmed with RM-NPC, not suitable for local treatment, who progressed after receiving first-line platinum-based chemotherapy (cohort 1) or immune checkpoint inhibitor immunotherapy with or without platinum-based chemotherapy (cohort 2), and who presented with measurable tumor lesions assessed by the Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Further inclusion criteria were adequate organ function as determined by: Absolute neutrophil count (ANC) ≥ 1.5 × 109/L; Platelet count ≥75 × 109/L; Hemoglobin ≥9 g/dL; serum total bilirubin (TBIL) ≤ 1.5 times the upper limit of normal (ULN); alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × upper limit of normal (ULN) (for subjects with liver metastases, TBIL ≤ 3 × ULN; ALT and AST ≤ 5 × ULN); Creatinine ≤1.5 × ULN or creatinine clearance rate ≥ 50 ml/min (Cockcroft-Gault formula); serum albumin ≥28 g/L; Thyroid-stimulating hormone (TSH) levels ≤1 × ULN; INR, APTT ≤ 1.5 × ULN, and a life expectancy of at least 3 month. Eligible patients were required to provide tumor tissue samples for biomarker analysis. Patients with any active autoimmune disease or history of autoimmune disease, a history of severe bleeding or any bleeding events with a serious grade of 3 or more, MRI showed that the tumor may have invaded important blood vessels or nasopharyngeal necrosis, or those who were previously treated with VEGFR inhibitors (anti­angiogenic small­molecule tyrosine kinase inhibitors, or anti­angiogenic monoclonal antibodies) were excluded. Full eligibility and exclusion criteria are included in the study protocol (available in the Supplementary Information file). The trial was approved by the Research Ethics Board of Sun Yat-sen University Cancer Center and was done in accordance with the Declaration of Helsinki. All patients provided written informed consent.