Biologics License Application Accepted for Vic-Trastuzumab Duocarmazine in HER2+ Advanced Breast Cancer

The FDA has accepted a biologics license application for vic-trastuzumab duocarmazine for patients with HER2-positive unresectable locally advanced or metastatic breast cancer.

The FDA has accepted a biologics license application (BLA) for vic-trastuzumab duocarmazine (SYD985) as a treatment for patients with HER2-positive unresectable locally advanced or metastatic breast cancer, according to a press release from Byondis.1

The BLA was based on findings from the phase 3 TULIP trial (NCT03262935), the results of which were presented at the 2021 European Society for Medical Oncology Congress. The trial investigated trastuzumab duocarmazine (n = 291), an anti-HER2 antibody drug conjugates, vs investigator choice chemotherapy (n = 146). A total of 437 patients were enrolled and were randomly assigned 2:1.2 Patients received 1.2 mg/kg of trastuzumab duocarmazine every 3 weeks or physicians choice chemotherapy. Treatment continued until progression or unacceptable toxicity.

The study’s primary end point of progression-free survival (PFS) was met, with a centrally reviewed median PFS of 7.0 months (95% CI, 5.4-7.2) reported in the trastuzumab duocarmazine arm vs 4.9 months (95% CI, 4.0-5.5) in the chemotherapy arm (HR, 0.64; 95% CI, 0.49-0.84; P = .002). An improvement in investigator assessed PFS was also observed in the trastuzumab duocarmazine arm of 6.9 months (95% CI, 6.0-7.2) vs 4.6 months (95% CI, 4.0-5.6) in the chemotherapy arm (HR, 0.60; 95% CI, 0.47-0.77; P <.001).

A Prescription Drug User Fee Act date has been set for May 12, 2023.

“Women with HER2-positive breast cancer generally have a more aggressive disease, greater likelihood of recurrence, and poorer prognosis,” Jan Schellens, MD, PhD, chief medical officer at Byondis, said in the press release. “Today's SYD985 [biologics license application] acceptance by the FDA is an important step forward toward our goal of providing a much-needed alternative for these patients.”

Median overall survival in the trastuzumab duocarmazine was 20.4 months compared with 16.3 months in the chemotherapy arm (HR, 0.83; 95% CI, 0.62-1.09; P = .153) and did not meet statistical significance. Moreover, there was no statistically significant difference in terms of health-related quality of life.

The most common adverse effects (AE) following treatment with trastuzumab duocarmazine included conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%) in the trastuzumab duocarmazine arm. Moreover, 7.6% of patients in the experimental arm developed interstitial lung disease or pneumonitis, with 2 patients experiencing a grade 5 events. Treatment discontinuation was necessary in 35.4% of patients in the trastuzumab duocarmazine arm—primarily due to AEs, the most frequent of which were eye disorders (20.8%) or respiratory disorders (6.3%).

“With our proprietary technologies, we aim to offer antibody-drug conjugates with a novel mechanism-of-action, which are still efficacious when other antibody-drug conjugate therapies have been exhausted,” Marco Timmers, PhD, chief executive officer at Byondis, concluded. “SYD985 combines a HER2-targeting antibody with a novel and potent cytotoxic drug in a way that limits damage to healthy tissue.”

The FDA had previously granted trastuzumab duocarmazine fast track designation in January 2018.3 The designation was based on findings from a first-in-human phase 1 trial (NCT02277717) that included a population of patients with HER2-positive metastatic disease that was heavily pretreated.

References

  1. FDA accepts Byondis' biologics license application for [vic-] trastuzumab duocarmazine (SYD985) in HER2-positive metastatic breast cancer. News Release. Byondis. July 12, 2022. Accessed July 12, 2022. https://prn.to/3auwhxq
  2. Manich CS, O’Shaughnessy J, Aftimos PG, et al. LBA15 – Primary outcome of the phase III SYD985.002/TULIP trial comparing [vic-]trastuzumab duocarmazine to physician’s choice treatment in patients with pre-treated HER-positive locally advanced or metastatic breast cancer. Annals of Oncol. 2021;23(suppl 15):S1283-S1346. doi:10.1016/annonc/annonc741
  3. Synthon’s [vic-]trastuzumab duocarmazine (SYD985) granted FDA fast track designation for pre-treated HER2-positive metastatic breast cancer. News Release. Byondis. January 25, 2018. Accessed July 12, 2022. https://bit.ly/3c9AbfJ