First china-manufactured proposed rituximab biosimilar met primary efficacy and safety endpoints in CD20-positive diffuse large B-cell lymphoma (generics)

Abstract

Background: While rituximab (rituximab) has revolutionized the treatment of B-cell lymphoma (BCL), its high manufacturing cost and lack of lower-priced competition have driven up prices resulting in limited access to treatment for millions of patients. HLX01 was developed as a rituximab biosimilar with the potential to increase market competition and treatment accessibility. Methods: Upon successful demonstration of equivalence in safety, PK/PD in previouslytreated patients with CD20(+) BCL, we subsequently conducted a multi-center, doubleblind, randomized, parallel-control Phase 3 study comparing the primary efficacy in best objective response rate (ORR) and safety profiles for six 3-week cycle treatments of 375mg/m either HLX01 with cyclophosphamide, doxorubicin, vincristine and prednisone (H-CHOP) or rituximab CHOP (R-CHOP) in patients with treatment-naïve CD20+ diffuse large B cell lymphoma (DLBCL). Results: A total of 81 CD20(+) BCL patients who have reached complete response (CR) or CR uncertain (CRu) after treatment was randomized to receive a single infusion of 375mg/m either HLX01 (n = 40) or rituximab-CN (n = 41). The geometric means ratio for AUC0-91D and Cmax [90% CIs] were 0.90 [0.81-1.00] and 1.03 [0.95 -1.11], respectively. The baseline CD19+/CD20(+) B-cell counts were reduced and remained over 95% depletion for up to 91 days; safety profiles were similar in both treatment groups. Subsequently, a total of 407 CD20+ DLBCL patients was randomized; 402 patients (H-CHOP:199; R-CHOP:203) in the full analysis set (FAS) and 382 patients (H-CHOP:188; R-CHOP:194) in per protocol study (PPS) were evaluated. As compared H-CHOP with R-CHOP, the ORR analysis of the FAS was 92.5% and 92.0% with Δ (equivalence margin difference) of 0.3% [95% CI: -4.87% to 5.56%; p = 0.839] and the PPS was 94.1% and 92.8% with Δ of 1.4% [95% CI: -3.59% to 6.32%; p = 0.608], respectively. Number of AEs, SAEs and detection of anti-drug antibodies was comparable between H-CHOP and R-CHOP groups. Conclusions: We report successful demonstration of equivalence in, PK/PD, efficacy and safety between HLX01 and rituximab sourced from China. Furthermore, HLX01 does not demonstrate new safety signals in comparison with rituximab.