Phase III comparative results on rituximab and CT-P10 in low-tumor burden FL

On 1 November 2018, Michinori Ogura from Kasugai Municipal Hospital, Kasugai, Japan, and colleagues, published in The Lancet Haematology results from a phase III trial (NCT02260804) that compared the efficacy and safety of rituximab to a biosimilar (CT-P10) in follicular lymphoma (FL) patients.

In this global, randomized, double-blind, active-controlled, phase III trial, newly-diagnosed FL patients with low-tumor burden were assigned to either rituximab or its biosimilar CT-P10. Findings from trials in patients with rheumatoid arthritis and advanced-stage FL have indicated that the efficacy of CT-P10 is equivalent to rituximab. CT-P10, as a biosimilar is substantially cheaper than rituximab providing a great financial aid to patients. Thus, the investigators sought to evaluate whether CT-P10 is therapeutically similar to rituximab and whether it can be used in naive low-tumor burden FL. The primary endpoint of this study was the percentage of patients who achieved overall response by seven months in the intention-to-treat (ITT) population. Secondary endpoints including, overall survival (OS) and progression-free survival (PFS), will be reported after the completion of the study.

Study design

• Ongoing trial (2015–2018), among 112 centers globally (Europe, Asia-Pacific, North America and other)
• N = 258 patients with histologically-confirmed CD-20⁺ FL (Grade 1–3a) were randomly assigned by a computer program 1:1 to either CT-P10 (n = 130) or rituximab (US sourced; n = 128)
• Up to the seventh month of the trial, 92% and 88% of patients completed treatment in the CT-P10 and rituximab groups, respectively
• Dosing:
  • Weekly intravenous infusions of CT-P10: 375 mg/m² or rituximab: 375 mg/m² for four weeks
  • Patients with complete responses (CR), partial responses (PR), unconfirmed complete responses (CRu) or stable disease (SD) by the third month of treatment were eligible for CT-P10 or rituximab maintenance (375 mg/m² every eight weeks for six cycles)
  • Total maintenance did not exceed 12 cycles over two years
  • No dose modifications or omissions were allowed
• Median follow-up (range) = 6.25 (6.25–6.48) months

Results

• ITT-population:
  • An overall response by month seven was observed in 83% (n = 108/130) of patients in the CT-P10 arm and in 81% (n = 104/128) in the rituximab group (1.8% difference estimate; [90% CI, -6.43–10.20]; [95% CI, -8.22–11.53])
  • CR: CT-P10: 28% vs rituximab: 34%
  • CRu: CT-P10: 5% vs rituximab: 2%
  • PR: CT-P10: 51% vs rituximab: 46%
  • SD: CT-P10: 13% vs rituximab: 14%
  • Relapsed or progressive disease (PD): CT-P10: 0% vs rituximab: 3%
• Per-protocol population:
  • Overall response: CT-P10: 87% vs rituximab: 83% (3.5% difference estimate; [90% CI, -4.56 –11.56]; [95% CI, -6.28–13.01])
  • CR: CT-P10: 31% vs rituximab: 34%
  • CRu: CT-P10: 5% vs rituximab: 2%
  • PR: CT-P10: 51% vs rituximab: 48%
  • SD: CT-P10: 13% vs rituximab: 13%
  • Relapsed or PD: CT-P10: 0% vs rituximab: 3%
• Similar pharmacokinetics were observed for CT-P10 and rituximab with mean serum drug concentrations being similar between the two groups over seven months

Safety

• Similar frequency of treatment-emergent adverse events (TEAEs) were observed between CT-P10 and rituximab, with the most commonly reported ones being:
  • Infusion-related reactions (CT-P10, 31% vs rituximab, 29%; all Grade 1–2, except for one Grade 3 in the CT-P10 arm)
  • Upper respiratory tract infections (CT-P10, 12% vs rituximab, 11%)
  • Fatigue (CT-P10, 7% vs rituximab, 9%)
• Serious TEAEs were reported in 5% of patients in the CT-P10 group and 2% in the rituximab arm
• Two cases of study drug-related TEAEs were related to CT-P10 (myocardial infraction and constipation), while none were reported for rituximab
• By the cut-off (January 2018), two deaths were reported in the CT-P10 group (myocardial infraction and respiratory failure) after the completion of the four induction cycles and both patients had predisposing history
• Two patients in the CT-P10 group discontinued treatment due to TEAEs (myocardial infraction and dermatitis). No patient discontinued treatment in the rituximab group due to TEAEs

The results of this phase III trial indicate that CT-P10 is therapeutically similar to rituximab, with no significant differences in the number of patients achieving an overall response. According to the authors, the pharmacokinetic and safety profiles of rituximab and its biosimilar CT-P10 were comparable and thus, CT-P10 can be considered as an effective and safe alternative to rituximab in low-tumor burden, newly-diagnosed FL patients.