Jun Zhu1, Jifeng Feng2, Xinchuan Chen3, Tongyu Lin4, Junning Cao5, Yanyan Liu6, Yaozhong Zhao7, Jie Jin8, Haiwen Huang9, Jianda Hu10, Jun Luo11, Liling Zhang12, Hongwei Xue13, Qingyuan Zhang14, Yu Yao15
1 Beijing Cancer Hospital, 2 Jiangsu Cancer Hospital, 3 West China Hospital, 4 Sun Yat-sen University Cancer Hospital, 5 Fudan University Shanghai Cancer Hospital, 6 He Nan Cancer Hospital, 7 Institute of Hematology & Blood Hospital, 8 The First Affiliated Hospital, Zhejiang University, 9 The First Affiliated Hospital of Soochow University, 10 Fujian Medical University Union Hospital, 11 The First Affiliated Hospital of Guangxi Medial University, 12 Wuhan Union Hospital, 13 The affiliated Hospital of Medical College Qingdao University, 14 Harbin Medical University Cancer Hospital, 15 Jiangsu Henrui Medicine Co., Ltd
Background: Classical Hodgkin lymphoma (cHL) is characterized by chromosome 9p24.1 alterations (including amplification), leading to overexpression of the PD-L1/PD-L2 immune checkpoint ligands. This genetically determined dependence on the PD-1 pathway makes cHL an attractive target for PD-1 blockade treatment with the anti–PD-1 monoclonal antibody, SHR-1210. SHR-1210-II-204 is a phase 2 study designed to evaluate the efficacy and safety of SHR-1210 in Chinese patients with relapsed/refractory (R/R) cHL.
Methods: SHR-1210-II-204 (NCT03155425) is a multicenter, single-arm, phase 2 study of SHR-1210 in Chinese patients with R/R cHL: who relapsed after autologous stem cell transplantation (ASCT) or relapsed / refractory to at least 2 prior systemic treatment and ineligibility for ASCT. Patients received SHR-1210 at a fixed dose of 200 mg intravenously every 2 weeks. Response was assessed with CT/MRI and FDG-PET according to the 2014 Lugano Criteria for Malignant Lymphomas. The primary end point was ORR per blinded independent central review (BICR). All patients who received at least 1 dose of SHR-1210 were included in the analyses. Informed consent was obtained for all patients. The data cutoff date for these analyses was Mar 18, 2018 that is six months after the last patient received the first dose.
Results: 75 patients were enrolled between June 9, 2017, and September 18, 2017. All patients had refractory or relapsed cHL. Among of them, 66.7% had received ≥3 prior lines of systemic chemotherapy, 8% of patients had progressive disease after BV, and 12% of patients had progressive disease after ASCT. Per BICR, the ORR (95% CI) was 82.7% (72.2%–90.4%) and CRR was 26.7%. With a median of 15 treatment doses, the most common TRAEs were skin hemangioma (97.3%), fever (41.3%), white cell count decreased (25.3%), neutrophil count decreased (22.7%), hypothyroidism (21.3%), upper respiratory tract infection (20.0%), ALT increased (18.7%), anemia (17.3%), infusion-related reaction (14.7%), cough (10.7%) and TSH increased (10.7%). The most common grade 3/4 TRAEs were white cell count decreased (4.0%), lymphocyte count decreased (4.0%), γ-glutamyltransferase increased (2.7%), neutrophil count decreased (2.7%), neutropenia (1.4%), thrombocytopenia (1.0%), and diarrhea (1.0%).
Conclusions: These results from an on-going study in heavily pretreated R/R cHL patients demonstrate that PD-1 blockade with SHR-1210 has a manageable safety profile and promising antitumor activity.