Investigators said TX05 met pathologic complete response criteria for equivalence to the originator product, Herceptin. The biosimilar candidate also fell within objective response rate, immunogenicity, safety, and tolerability margins for similarity.
A phase 3 study of a trastuzumab biosimilar candidate (TX05) and reference product (Herceptin) has demonstrated equivalence in patients with human epidermal growth factor receptor 2 (HER2)-positive early stage breast cancer, according to findings presented at the European Society for Medical Oncology Congress 2021.
The trial enrolled patients (N = 809) in the neoadjuvant, or presurgery, setting. Of those, 674 were evaluable. The primary end point was therapeutic equivalence based on pathologic complete response (pCR), or absence of residual cancer, following neoadjuvant chemotherapy.
Secondary end points were objective response rate (ORR), immunogenicity, safety, and tolerability.
Patients were recruited at 124 treatment centers in 10 countries, including Russia, Hungary, Chile, and India. They received four 3-week cycles of epirubicin and cyclophosphamide and were then randomized to four 3-week cycles of paclitaxel and TX05 or the reference biosimilar (TRA, as available in the European Union). Investigators said close to 100% of patients completed all planned cycles of trastuzumab therapy.
They said the proportions of patients meeting pCR criteria for equivalence were “highly similar” between the TX05 (48.8%) and TRA (45.3%) cohorts (risk ratio, 1.0783).
They also said equivalence was observed when patients from both cohorts were stratified according to cancer stage and Eastern Cooperative Oncology Group (ECOG) performance status. ECOG is a means of classifying patients according to the level of disability they suffer as a result of their cancer, with zero representing the highest functionality.
ORR was also highly similar between the TX05 (84.3%) and TRA (85.0%) groups, and findings for patients with complete response, partial response, and stable disease were also highly similar between cohorts. The same was true for pharmacodynamics, authors of the study said.
“In all sensitivity analyses, including a 'tipping point' analysis, the 95% CI of the risk ratio was completely contained within the predefined interval,” they wrote.
Safety analysis of treatment-emergent adverse events (TEAEs) was confined to cycles 5 through 8 of the treatment, as this was the period during which patients received trastuzumab. The investigators said 62.4% of patients experienced TEAEs with TX05 vs 62.5% of patients with TRA, which they said was similar and demonstrative of biosimilarity for TX05.
The most common TEAEs were musculoskeletal and connective tissue disorders, nervous system and gastrointestinal disorders, general disorders, and investigative-related and administration-site conditions.
“Overall, the TX05 study treatment was well tolerated. The safety profile was consistent with the known profile of TRA with no significant safety findings seen in the study,” the authors wrote.
“The results of this study support that there is no clinically meaningful difference between TX05 and [TRA],” they said, adding that based on pharmacokinetic similarity, it was possible to conclude that TX05 is also highly similar to the US version of reference trastuzumab.
The study was sponsored by Tanvex BioPharma USA, which is the company developing TX05 for market.
Preliminary results from the phase 3 study concerning just pCR were released in February 2021.
Krivorotko P, Manikhas A, Moiseenko F, et al. Trial comparing the safety, efficacy, and immunogenicity of trastuzumab biosimilar candidate (TX05) with originator trastuzumab in HER2+ early breast cancer. Presented at ESMO Congress 2021; September 17-21, 2021. ePoster 127P.