Safety and activity of sintilimab in patients with relapsed or refractory classical Hodgkin lymphoma (ORIENT-1): a multicentre, single-arm, phase 2 trial

Background Sintilimab (Innovent Biologics, Suzhou, China), a highly selective, fully humanised, monoclonal antibody, blocks the interaction between PD-1 and its ligands. We aimed to assess the activity and safety profile of sintilimab in Chinese patients with relapsed or refractory classical Hodgkin lymphoma. Methods In this ongoing, single-arm, phase 2 study, we recruited patients with histopathologically diagnosed classical Hodgkin lymphoma that was relapsed or refractory after two or more lines of therapy from 18 hospitals in China. Patients were given intravenous sintilimab (200 mg, once every 3 weeks) until progression, death, unacceptable toxicity, or withdrawal of consent. The primary outcome was the proportion of patients in the full analysis set (ie, those with classical Hodgkin lymphoma confirmed by the central pathology laboratory) who had an objective response, as assessed by an independent radiological review committee (IRRC), by 24 weeks after enrolment of the last patient. Tumour response was assessed by enhanced CT scan or MRI at baseline, at weeks 6, 15, and 24, every 12 weeks from weeks 24 to 48, and every 16 weeks beyond week 48. Safety was assessed in all treated patients. This study is registered with ClinicalTrials.gov, number NCT03114683, and is ongoing. Findings Between April 19, 2017, and Nov 1, 2017, 96 patients were enrolled and commenced treatment. Four patients, whose diagnosis was not subsequently confirmed by the central pathology laboratory, were excluded from the full analysis set. Ten patients discontinued treatment. Median duration of follow-up was 10·5 months. In the full analysis set (n=92), 74 patients (80·4%; 95% CI 70·9–88·0) had an IRRC-assessed objective response before the analysis cutoff date of April 16, 2018. 89 (93%) of 96 patients had treatment-related adverse events, and 17 patients (18%) had grade 3 or 4 treatment-related adverse events, the most common being pyrexia (three [3%] patients). 14 (15%) patients had serious adverse events of any cause. No patient died during the study. Interpretation Sintilimab could be a new treatment option for patients with relapsed or refractory classical Hodgkin lymphoma in China. Funding Innovent Biologics, Eli Lilly and Company, National New Drug Innovation Programme, and the National Key Scientific Programme Precision Medicine Research Fund of China.