TX05 Provides Comparable DFS Benefit to Trastuzumab in Early-Stage HER2+ Breast Cancer

Adjuvant treatment with TX05 resulted in a similar disease-free survival (DFS) benefit to that of trastuzumab (Herceptin) in patients with early-stage HER2-positive breast cancer, according to results from the phase 3 TX05-03e trial (NCT04109391) presented during the 2022 ASCO Annual Meeting.¹

Findings showed that in patients who received neoadjuvant TX05 followed by adjuvant TX05 (n = 175), DFS events occurred in 3.4% of patients compared with 3.7% in those who received neoadjuvant trastuzumab followed by adjuvant TX05 (n = 81) and 6.7% in those who were given neoadjuvant trastuzumab followed by adjuvant trastuzumab (n = 82).

“The rates of DFS, overall survival [OS] adverse effects [AEs], and immunogenicity were similar across treatment groups and continue to support the conclusion of biosimilarity of TX05 to [trastuzumab],” lead study author Petr Krivorotko, MD, PhD, a professor in the Oncology Department of I.I. Mechnikov North-Western State Medical University, and head of the Department of Breast Surgical Oncology and a leading researcher in the Research Division of Breast Cancer at N.N. Petrov Institute of Oncology in St. Petersburg, Russia, and colleagues, wrote in a poster presentation.

TX05 has been developed as a biosimilar to trastuzumab, which is a standard treatment in patients with early-stage HER2-positive breast cancer. Previous results from the phase 3 TX05-03 trial (NCT03556358) supported the therapeutic equivalence of adjuvant TX05 plus paclitaxel and adjuvant trastuzumab plus paclitaxel.

The TX05-03e trial aimed to further verify the findings by comparing single-agent TX05 with trastuzumab. The study enrolled patients who were at least 18 years of age who had early-stage HER2-positive breast cancer and who received neoadjuvant treatment with TX05 or trastuzumab.² Patients were required to undergo successful surgical resection of their primary tumor, have no evidence of residual disease and have not received any other adjuvant therapy.

Notably, patients with hormone receptor–positive breast cancer were permitted to receive hormonal therapy, and premenopausal patients needed to have a negative serum pregnancy test within 14 days of first administration of study drug.

Key exclusion criteria included breast cancer metastases or residual disease following surgery, had a history of a medical condition that could increase risk of study treatment, or were lactating or pregnant.

Patients who received neoadjuvant TX05 continued adjuvant treatment with 8 mg/kg of TX05 in the first cycle, followed by 6 mg/kg of TX05 in cycles 2 through 13. Patients given neoadjuvant trastuzumab were randomized 1:1 to receive adjuvant TX05 at the same dosing regimen, or adjuvant trastuzumab at 8 mg/kg in cycle 1 and 6 mg/kg in cycles 2 to 13. All treatments were administered once every 3 weeks.

The primary objectives of the trial were to measure DFS and OS. Safety evaluation included treatment-emergent AEs, serious AEs, death, laboratory parameters, vitals, echocardiogram, left ventricular ejection fraction, and physical examination. Immunogenicity was also evaluated.

Krivorotko noted that demographic and baseline characteristics were similar in patients across all 3 arms of the study.

Regarding safety, any-grade AEs occurred in 53.1% of those who received TX05 followed by TX05, 56.1% of those who received trastuzumab followed by trastuzumab, and 37% of those who were given trastuzumab followed by TX05.

Krivorotko added that the frequency, type, and severity of related AEs were similar between the 3 arms, and no new safety signals were detected.

One death was reported in the trastuzumab/TX05 arm due to disease progression.

References

1. Krivorotko P, Manikhas A, Poddubskaya E, et al. TX05-03e: Adjuvant treatment following neoadjuvant treatment and surgical resection in TX05-03, a trial comparing the safety, efficacy, and immunogenicity of trastuzumab biosimilar candidate (TX05) with originator trastuzumab in HER2+ EBC. J Clin Oncol. 2022;40(suppl 17):LBA511. doi:10.1200/JCO.2022.40.17_suppl.LBA511
2. Extension study to provide adjuvant treatment following neoadjuvant treatment and surgical resection in protocol TX05-03. ClinicalTrials.gov. Updated April 26, 2022. Accessed June 24, 2022. https://clinicaltrials.gov/ct2/show/NCT04109391