The Phase III TULIP study met its primary endpoint of progression-free survival (PFS), demonstrating a statistically significant improvement of its [Vic-]Trastuzumab Duocarmazine (SYD985) over physician’s choice, said the developer.
PFS is defined as the time from the date of randomization to the date of first documented disease progression or death due to any cause, whichever occurred earlier. The study also demonstrated preliminary supportive overall survival (OS) results, reported Byondis.
The Nijmegen, Netherlands headquartered company did not provide detailed data along with the topline results of the trial today but confirmed it would release further information from the TULIP study at scientific conferences in due course.
“There is considerable unmet medical need in patients with HER2-positive metastatic breast cancer and [vic-]trastuzumab duocarmazine represents a promising potential clinical advance,” said Byondis Chief Medical Officer, Jan Schellens. “We are excited by the topline results of TULIP."
Meanwhile, it is finalizing its biological license application (BLA) on SYD985 and said it intends to submit that before the end of 2021.
In addition, given the positive study outcome, Byondis said it is now planning to explore partnerships with pharma and biopharma companies in order to commercialize SYD985.
SYD985 was granted fast track designation by the US Food and Drug Administration (FDA) in January 2018 based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part Phase I clinical trial.
The study outline
Begun in November 2017, TULIP enrolled a total of 436 female patients aged 18 and over, at 83 sites across the US, Canada, Europe and Singapore. To qualify, patients had either: progression during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease; or progression during or after ado-trastuzumab emtansine treatment.
Patients were randomly assigned (2:1) to receive SYD985 or physician's choice treatment until disease progression or unacceptable toxicity.
In addition to blinded, independent, centrally reviewed PFS, the trial’s secondary objectives were to compare the two treatment groups with respect to: (1) overall survival (OS); (2) objective response rate (ORR) on the basis of the blinded independent central review; (3) investigator-assessed PFS; (4) patient-reported outcomes (PRO) for health-related quality of life; and (5) safety and tolerability.
Byondis' ADC, [Vic-]Trastuzumab Duocarmazine (SYD985) is comprised of the monoclonal antibody trastuzumab and a cleavable linker-drug called valine-citrulline-seco-DUocarmycin-hydroxyBenzamide-Azaindole (vc-seco-DUBA).
The company explained that 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.