FDA Accepts BLA for [Vic-] Trastuzumab Duocarmazine as HER2+ mBC Treatment

Based on findings from the TULIP study, [vic-] trastuzumab duocarmazine may be a new standard treatment option for patients with HER2-positive unresectable locally advanced metastatic breast cancer. a biologics license application has been accepted by the FDA.

The FDA has accepted the biologics license application for [vic-] trastuzumab duocarmazine (SYD985) for the treatment of patients with HER2-positive unresectable locally advanced or metastatic breast cancer (mBC), according to an announcement by Byondis B.V.1

[Vic] trastuzumab duocarmazine is an investigational next-generation anti-HER2 antibody-drug conjugate that was previously granted fast track designation by the FDA. Acceptance of the BLA by the regulatory body was based on data from the phase 3 TULIP multi-center, open-label, randomized clinical trial (NCT03262935), in which [vic] trastuzumab duocarmazine demonstrated a statistically significant improvement in progression-free survival (PFS) of 2.1 months over physician’s choice of therapy. The study met its primary end point and the application has been given a Prescription Drug User Fee Act target action day of May 12, 2023.

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

In the TULIP study, 436 patients who had either progression during or after at least 2 HER2-targeting treatment regimens for locally advanced or metastatic disease or progression during or after (ado-)trastuzumab emtansine treatment were included. Patients were randomized 2:1 to receive either [vic-] trastuzumab duocarmazine every 3 weeks or physician’s choice of either lapatinib (Tykerb), capecitabine, trastuzumab (Herceptin), vinorelbine, or eribulin.2

Secondary end points explored during the study included overall survival (OS), objective response rate (ORR), investigator-assessed PFS, and patient-reported outcomes for health-related quality of life.

According to blinded central review, the median PFS with [vic-] trastuzumab duocarmazine was 7.0 months (95% CI, 5.4-7.2) compared with 4.9 months (95% CI, 4.0-5.5) with physician’s choice of therapy (HR, 0.64 95% CI, 0.49-0.84; P = 0.002). In terms of the investigator-assessed PFS, treatment with [vic-] trastuzumab duocarmazine was also significantly improved compared with the control at 6.9 months (95% CI, 6.0-7.2) vs 4.6 months (95% CI, 4.0-5.6), respectively (HR, 0.60; 95% CI, 0.47-0.77; P <0.001).3

The first analysis of the TULIP study also revealed that [vic-] trastuzumab duocarmazine achieved an improvement in OS vs physician’s choice of therapy (HR, 0.83; 95% CI, 0.62-1.09]; P = 0.153). There was no significant difference between the 2 arms in terms of the secondary end point of ORR.

In regard to safety, the most frequently reported adverse events (AEs) in the [vic-] trastuzumab duocarmazine arm were conjunctivitis (38.2%), keratitis (38.2%), and fatigue (33.3%). In the physician’s choice arm, the most common AEs were diarrhea (35.8%), nausea (31.4%), and fatigue (29.9%). Cases of interstitial lung disease and pneumonitis were reported in 7.6% of patients treated in the experimental arm, of which 5.6% were grade 1 or 2 in severity. Two of the interstitial lung disease/pneumonitis events were grade 5. AEs that lead to discontinuation of treatment in either arm were eye disorders (20.8%), or respiratory disorders (6.3%). Treatment discontinuation occurred in 35.4% of patients in the experimental arm vs 10.2% in the control arm.

Based on findings from the TULIP study, [vic-] trastuzumab duocarmazine may be a new standard treatment option for patients with HER2-positive unresectable locally advanced mBC.

"With our proprietary technologies, we aim to offer antibody-drug conjugates with a novel mechanism-of-action, which are still efficacious when other ADC therapies have been exhausted," said Marco Timmers, PhD, chief executive officer of Byondis, in a statement.1 "SYD985 combines a HER2-targeting antibody with a novel and potent cytotoxic drug in a way that limits damage to healthy tissue."


1. FDA accepts Byondis' biologics license application for [vic-] trastuzumab duocarmazine (SYD985) in HER2-positive metastatic breast cancer. News release. Byondis B.V. July 12, 2022. Accessed July 12, 2022. https://bit.ly/3yBQ5ak

2. SYD985 vs. physician's choice in participants with HER2-positive locally advanced or metastatic breast cancer (TULIP). Clinicaltrials.gov. Updated March 9, 2022. Accessed July 12, 2022. https://clinicaltrials.gov/ct2/show/NCT03262935

3. Manich S, 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 HER2-positive locally advanced or metastatic breast cancer. Ann Oncol. 2021l32(5): S1288. doi: 10.1016/j.annonc.2021.08.2088