Trastuzumab duocarmazine improves survival in HER2 breast cancer

Trastuzumab duocarmazine improves survival in HER2 breast cancer

Netherlands-based pharmaceutical company Byondis has announced positive topline results from the phase III TULIP study of its antibody-drug conjugate [vic-]trastuzumab duocarmazine in patients who were pretreated for HER2-positive unresectable locally advanced or metastatic breast cancer (MBC).

The study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement over physician’s choice. PFS is defined as the time from the date of randomisation to the date of the first documented disease progression or death due to any cause. The study also demonstrated preliminary supportive overall survival (OS) results.

TULIP study enrolled a total of 436 female patients aged 18 and over, at 83 sites across the United States, Canada, Europe and Singapore. To qualify, patients had either: (1) progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease; or (2) progression during or after ado-trastuzumab emtansine treatment.

Patients were randomly assigned (2:1) to receive [Vic-]Trastuzumab Duocarmazine or physician’s choice treatment until disease progression or unacceptable toxicity.

[Vic-]Trastuzumab duocarmazine incorporates Byondis’ distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. Although in general, marketed antibody-drug conjugates have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still need for improvement.

Byondis’ antibody-drug conjugate -[vic-]trastuzumab duocarmazine is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA). The antibody part of [vic-]trastuzumab duocarmazine binds to HER2 on the surface of the cancer cell and the ADC is internalised by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumour cell death. Thus the drug is considered as a form of targeted chemotherapy.