Title: Efficacy, pharmacokinetics, and safety of the biosimilar CT-P10 compared with rituximab in patients with previously untreated advanced-stage follicular lymphoma: a randomised, double-blind, parallel-group, non-inferiority phase 3 trial

Kim, WS et al.


What You Need to Know:

According to results of a phase 3 study, CT-P10, a rituximab biosimilar, demonstrates non-inferior efficacy, pharmacokinetic equivalence, and a comparable safety profile to rituximab in patients with advanced-stage follicular lymphoma.

Trial Design:

  • Double-blind, ongoing phase 3 study evaluated the “non-inferior efficacy and pharmacokinetic equivalence of CT-P10 compared with rituximab, when used in combination with cyclophosphamide, vincristine, and prednisone (CVP) in patients with newly diagnosed advanced-stage follicular lymphoma”
  • 140 adult patients with Ann Arbor stage III-IV follicular lymphoma were randomized (1:1) to receive CVP in addition to 375 mg/m2 of intravenous CT-P10 or rituximab; treatment was administered on day 1 of 21-day cycles and was continued for a total of 8 cycles
  • Equivalence of pharmacokinetics: “shown if the 90% CIs for the geometric mean ratio of CT-P10 to rituximab in AUCτ and CmaxSS were within the bounds of the equivalence margin of 80% and 125%”
  • Non-inferiority of response: “shown if the one-sided 97·5% CI lay on the positive side of the −7% margin, using a one-sided test done at the 2·5% significance level”
  • Primary efficacy endpoint: percent of patients with an overall response over 8 cycles; analysis included all randomized patients
  • Primary pharmacokinetic endpoint: AUCτ (area under the concentration-time curve at steady state), CmaxSS at cycle 4 (maximum serum concentration at steady state); analysis included patients in the pharmacokinetic subset population

Key Outcomes:

  • Eight-cycle induction period data reported (to week 24 of the study)
  • Patients in the efficacy population with an overall response: 97.0% in the CT-P10 group (64/66) vs 92.6% in the rituximab group (63/68) (4.3%; one-sided 97.5% CI: -4.25)
  • Ratio of geometric least squares means (CT-P10/rituximab) for AUCτ: 102.25% (90% CI: 94.05, 111.17)
  • Ratio of geometric least squares means (CT-P10/rituximab) for CmaxSS: 100.67% (90% CI: 93.84, 108.00)
  • Treatment-emergent adverse events: experienced by 83% of CT-P10 patients (58/70) vs 80% of rituximab patients (56/70)
  • Neutropenia was the most common grade 3 or 4 treatment-emergent adverse event (experienced by 21% of CT-P10 patients [15/70] vs 10% of rituximab patients [7/70])
  • 23% of CT-P10 patients (16/70) experienced ≥1 treatment-emergent serious adverse event vs 13% of rituximab patients (9/70)