Phase 1 trial of HS006, a recombinant human-mouse chimeric anti-CD20 monoclonal antibody to treat CD20 positive B-cell non-Hodgkin's lymphoma in China

In a phase 1 dose escalating clinical trial, the tolerability and efficacy of HS006, a recombinant human-mouse chimeric anti-CD20 monoclonal antibody, for the treatment of CD20 positive B-cell non-Hodgkin's lymphoma (NHL) was investigated.The dosage of HS006 was escalated in eligible patient groups at 250 mg/m 2 (n = 3), 375 mg/m 2 (n = 4), 500 mg/m 2 (n = 4) and 625 mg/m 2 (n = 3) doses, given once a week as a single-dose with a 35-day follow-up, and 4 once a week multiple-doses with a 168-day follow-up.Dose-limiting toxicity (DLT) or a maximum tolerated dose were not found.All patients reported at least one treatment emergent adverse events (TEAEs), from which 11 were drug-related TEAEs, with the most common being lymphocytopenia (9, 64.3%), leukopenia (5, 35.7%), upper respiratory infection (5, 35.7%), and rash (4, 28.6%).There were 6 (42.9%) patients with grade 3 or 4 TEAEs, among which drug-related TEAEs were 4 cases of grade 3 lymphocytopenia.The plasma concentration of HS006 as well as Cmax, Cav,ss and AUC showed a dose dependent increasing trend with accumulating effects after multiple-doses.The objective response rate was 14.3% (95% CI: 1.92-45.45%),with 1 follicular lymphoma patient (375 mg/m 2 ) achieving complete response and 1 diffuse large B cell lymphoma patient (625 mg/m 2 ) achieving partial response.Depletion of CD19+ B cells was detected until the end of follow-up in the 4 dose groups.HS006 exhibited well tolerance in CD20-positive B-cell NHL patients in China at dose levels of 250, 375, 500 and 625 mg/m 2 , with no serious hematologic drug-related TEAEs and no DLT reported.