Byondis ESMO Late-Breaking Presentation Confirms ADC [Vic-] Trastuzumab Duocarmazine (SYD985) Superior to Physician's Choice in Pre-treated Locally Advanced or Metastatic HER2-Positive Breast Cancer - Seite 2

More TULIP (SYD985.002) Results

Starting in November 2017, TULIP enrolled 437 female patients with a median age of 56 and a median of 4 prior MBC treatments. The study was conducted at 83 sites in 11 countries 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 SYD985 (n=291, 1.2 mg/kg q three weeks) or PC chemotherapy (n=146) until disease progression or unacceptable toxicity. The trial was powered to detect a Hazard Ratio (HR) of 0.65 at the P < 0.05 significance level.

The study's primary endpoint, blinded centrally reviewed median PFS, was 7.0 months (5.4-7.2, 95% CI) for SYD985 and 4.9 months (4.0-5.5) for PC (HR 0.64 [0.49-0.84], p = 0.002). Secondary endpoint results are as follows: investigator-assessed PFS significantly improved, 6.9 months (6.0-7.2) versus 4.6 months (4.0-5.6) for PC (HR 0.60 [0.47-0.77], p < 0.001); OS first analysis indicated HR was 0.83 (0.62-1.09, p = 0.153); and no significant differences were observed in objective response rate (ORR) or health-related quality of life (HRQoL).

The most frequently reported adverse events (AEs) for SYD985 were conjunctivitis (38.2%), keratitis (38.2%) and fatigue (33.3%). For PC, the most frequently reported AEs were diarrhea (35.8%), nausea (31.4%) and fatigue (29.9%). Interstitial lung disease/pneumonitis was reported for 7.6% of patients treated with SYD985. AEs leading to discontinuation of treatment were 35.4% and 10.2% in the SYD985 and PC groups, respectively. In the SYD985 group, these were mainly related to eye disorders (20.8%) or respiratory disorders (6.3%).

[Vic-]Trastuzumab Duocarmazine (SYD985), a Next Generation Antibody-Drug Conjugate

[Vic-]trastuzumab duocarmazine (SYD985) incorporates Byondis' distinctive, proprietary duocarmazine linker-drug (LD) technology ByonZine. Although in general, marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still need for improvement.

The ADC [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 internalized by the cell. After proteolytic cleavage of the linker, the inactive cytotoxin is activated and DNA damage is induced, resulting in tumor cell death. SYD985 is considered a form of targeted chemotherapy.