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
- 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
- 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
- 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
Treatment Combinations for HER2-Positive Breast Cancer
March 7th 2013As part of our coverage for the 30th Annual Miami Breast Cancer Conference, we bring you an interview with Dr. Mark Pegram, director of the breast cancer program at the Stanford Women’s Cancer Center and codirector of the molecular therapeutics program. Dr. Pegram will be discussing the potential for novel HER2 combination therapies at the conference.
