This study compared the efficacy, safety and immunogenicity of ripertamab (SCT400) and rituximab (Mabthera® ) combined with CHOP as the first-line treatment for Chinese patients with CD20-positive diffuse large B cell lymphoma (DLBCL). This is a randomized, patient-blind, multicenter, active-control, non-inferiority study with parallel design. Patients were randomly (2:1) to receive ripertamab combined with CHOP (S-CHOP) or rituximab (Mabthera® ) combined with CHOP (R-CHOP) for up to 6 cycles. The primary endpoint was the Independent Review Committee (IRC) assessed objective response rate (ORR). A total of 364 patients (243 in the S-CHOP and 121 in the R-CHOP groups) were eligible for the study. IRC-assessed ORRs were 93.8% (95% confidence interval [CI] 90.0%, 96.5%) and 94.2% (95% CI: 88.4%, 97.6%) in the S-CHOP and R-CHOP groups, respectively. The ORR difference between the two groups -0.4% (95% CI: -5.5%, 4.8%) met the pre-specified non-inferiority margin of -12%. There were no significant differences between the S-CHOP and R-CHOP groups in 1-year event-free survival rates (56.2% and 58.1%, p=0.8005), 1-year progression-free survival rates (81.1% and 83.2%, p=0.8283), and 3-year overall survival rates (81.0% and 82.8%, p=0.7183). The rates of adverse events (AEs) and ≥ grade 3 AEs were 97.9% and 99.2%, 85.2% and 86.0% in the S-CHOP and R-CHOP groups, respectively. The percentage of anti-drug antibodies positive patients in the S-CHOP group was numerically lower than the R-CHOP group (10.9% vs. 16.0%). This study demonstrated that S-CHOP was not inferior to R-CHOP in the first-line treatment of CD20-positive DLBCL Chinese patients in efficacy, safety and immunogenecity. S-CHOP could be an alternative first-line treatment for DLBCL, and was expected to be a cost-effective alternative to rituximab and offer an opportunity to increase access to the biologics. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.