166MO - A phase III trial to compare the efficacy, safety, pharmacokinetics and immunogenicity of HD201 to trastuzumab in HER2+ early breast cancer patients (TROIKA)

Background

HD201, developed by Prestige Biopharma Ltd is a biosimilar candidate to Herceptin. TROIKA is a randomised, double-blind, parallel-group, equivalence, multicentre Phase III study designed to compare the efficacy, safety, pharmacokinetics (PK) and immunogenicity of HD201 to Herceptin in patients with HER2 positive early breast cancer (EBC).

Methods

503 patients with HER2+ EBC were randomised in a 1:1 ratio to receive either HD201 or Herceptin in neoadjuvant settings for 8 cycles in combination with chemotherapy (4 cycles of docetaxel followed by 4 cycles of epirubicin/cyclophosphamide). The patients then underwent surgery followed by 10 cycles of HD201 or Herceptin monotherapy. The primary objective was to demonstrated equivalence in total pathologic complete response (tpCR) rate between treatments. The pre-specified equivalence margins were +/- 15% for the 95% confidence interval of the absolute difference for tpCR rates. Secondary endpoints including breast pathologic complete response (bpCR), overall response rate (ORR), event-free survival (EFS), PK, immunogenicity, and safety were assessed.

Results

The tpCR rates were 46.60% and 46.20% for HD201 and Herceptin respectively. The difference of tpCR rate was 0.50% and the 95% CI was -8.6% - 9.6%, both contained within the pre-defined equivalence margins. Secondary endpoints were similar between HD201 and Herceptin. The bpCR rate of 55.00% and 53.40% and the ORR of 90.80% and 89.40% for HD201 and Herceptin respectively. Safety was comparable between HD201 and Herceptin during neoadjuvant period. PK equivalence was demonstrated with mean steady-state C_trough levels of 53.72 ug/mL in the HD201 group and 51.64 ug/mL in the Herceptin group at the onset of Cycle 8, providing a 4.0% [-2.6%; 10.6%] on the mean relative difference between the two treatments within the pre-specified interval [-20%;+20%]. Interim data indicate comparable immunogenicity between HD201 and Herceptin.

Conclusions

Equivalence in efficacy, safety, PK and immunogenicity profiles was demonstrated between HD201 and Herceptin. TROIKA is currently in its follow up phase. Complete safety, immunogenicity and survival data are to follow.

Clinical trial identification

Eudract: 2016-004019-11.

Editorial acknowledgement

Legal entity responsible for the study

Prestige Biopharma Ltd.

Funding

Prestige Biopharma Ltd.

Disclosure

All authors have declared no conflicts of interest.