CT-P10 versus reference rituximab in combination with CVP in advanced-stage follicular lymphoma: Phase 3, double-blind, randomized trial

Abstract

Background: CT‐P10 is the first biosimilar of innovator rituximab (RTX) approved for all indications by the EMA. CT‐P10 has demonstrated PK and efficacy equivalence in rheumatoid arthritis (Yoo et al. Am College Rheumatol Ann Meeting 2016; abstr. 1635). This study aimed to demonstrate non‐inferiority (NI) of efficacy and PK equivalence between CT‐P10 and RTX innaive AFL. Methods: A total of 140 patients were randomized in a 1:1 ratio to receive CT‐P10 or RTX (375 mg/m2 i.v) plus CVP (cyclophosphamide, vincristine and prednisone) every 3 weeks over 8 cycles. Overall response rate (ORR) according to the 1999 IWG criteria was assessed by the independent review committee. Results: ORR of 97.0% and 92.6% and CR/CRu of 39.4% and 33.8% for CT‐P10 and RTX groups, respectively, were observed after 8 cycles of therapy. Based on the ORR, the therapeutic NI of CT‐P10 to RTX was demonstrated as the difference between the two groups was 4.3% and the one‐sided 97.5% CI (‐4.25%) was greater than the predefined NI margin (‐7%). At the median follow‐up of 17 months, 10 patients in the CT‐P10 group and 13 patients in the RTX group experienced disease progression or death. There was no statistically significant difference of PFS between the two groups (P‐value: 0.4802, Hazard Ratio: 0.92 [95% CI 0.325‐1.698]). B‐cell depletion was comparable from after the 1st infusion and up to the 8th cycle. Overall safety profile of CT‐P10 was consistent with that of RTX (Table) and the proportion of patients with positive anti‐drug antibody were similar between the two groups (4.3% and 2.9%) over 24 weeks. No progressive multifocal leukoencephalopathy or Hepatitis B virus reactivation was reported in both groups. Table: 318O Safety profile over 24 weeks CT‐P10 N (%) (N=70) RTX (N=70) TEAE related to the study drug Treatment‐emergent adverse event (TEAE)* Serious TEAE* Infusion‐related reaction* Infection* 37 (52.9) 34 (48.6) 6 (8.6) 4(5.7) 15 (21.4) 17 (24.3) 6 (8.6) 9(12.9) *Difference between groups is not statistically significant. Conclusions: This study demonstrated therapeutic NI ofCT‐P10 to RTX plus CVP in previously untreated AFL. CT‐P10 was well‐tolerated and the safety profile including immunogenicity of CT‐P10 was comparable to that of RTX over 8 cycles.