Synthon Biopharmaceuticals (Synthon) has announced that the US Food & Drug Administration (FDA) has granted Fast Track designation for its investigational anti-HER2 antibody-drug conjugate (ADC) [vic-] trastuzumab duocarmazine (SYD985). This designation is for treating patients diagnosed with HER2-positive metastatic breast cancer (MBC) that has progressed during or after at least two HER2-targeting treatment regimens for locally advanced or metastatic disease, or progressed during or after [ado-]trastuzumab emtansine treatment.
The US FDA Fast Track designation is one of four programs that are intended to facilitate and expedite development and review of new drugs to address unmet medical need in the treatment of a serious or life threatening condition.
Fast Track designation for [vic-]trastuzumab duocarmazine was granted based on promising data from heavily pre-treated last-line HER2-positive MBC patients participating in a two-part phase I clinical trial (SYD985.001). The positive clinical results indicate that this HER2-targeting ADC is efficacious and safe and could therefore provide substantial benefit to patients with no other treatment options.
In November 2017, Synthon initiated the pivotal phase III TULIP trial, a multi-center, open-label, randomized clinical trial comparing the efficacy and safety of the ADC
[vic-]trastuzumab duocarmazine to physician's choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Patients are currently being enrolled in this trial, which will be conducted in up to 100 sites in the United States, Canada, Europe and Singapore.
Dr. Jacques Lemmens, chief executive officer of Synthon, commented: “We are very pleased with this Fast Track designation for [vic-]trastuzumab duocarmazine based on the promising phase I data. There is a high unmet medical need in patients that have HER2-positive MBC and have progressed on trastuzumab and [ado-]trastuzumab emtansine. I believe that the benefit/risk balance of [vic-]trastuzumab duocarmazine is favorable and that it can provide extended benefit to these patients. Fast Track designation will support efficient development and review of [vic-]trastuzumab duocarmazine and enable early access of this promising new single-agent therapy option.”
Trial SYD985.002 (or TULIP) is a multi-center, open-label, randomized clinical Trial comparing the efficacy and safety of the antibody-drUg conjugate [vic-]trastuzumab duocarmazine (SYD985) to physician's choice in HER2-positive unresectable Locally advanced or metastatIc breast cancer Patients.
Primary objective is to demonstrate that [vic-]trastuzumab duocarmazine is superior to physician’s choice in prolonging progression-free survival (PFS) on the basis of the blinded independent central review of tumor assessment. Secondary objectives are to compare the two treatment groups with respect to overall survival (OS); objective response rate (ORR) on the basis of the blinded independent central review; Investigator assessed PFS; patient-reported outcomes (PRO) for health related quality of life (EORTC QOL C30 & BR23); safety and tolerability.
This trial is registered in ClinicalTrials.gov with identifier NCT03262935.
Trial SYD985.001 is a two part first-in-human study with the anti-HER2 ADC SYD985 to evaluate the safety, pharmacokinetics and efficacy in patients with histologically-confirmed, locally advanced or metastatic tumors. These are patients who have progressed on standard therapy or for whom no standard therapy exists.
During part I (dose escalation) patients with solid tumors of any origin were enrolled. For part II (expanded cohorts) enrollment was focused at patients with breast or selected non-breast tumors with demonstrated HER2 expression including HER2-low expressing (IHC 1+/2+, ISH-) tumors and measurable disease as per RECIST 1.1.
Preliminary results of the trial were presented at the San Antonio Breast Cancer Symposium in December 2016 (Abstract P6-12-02; SYD985, a novel anti-HER2 ADC, shows promising activity in patients with HER2-positive and HER2-negative metastatic breast cancer. Aftimos PG, van Herpen CM, Mommers EC, Koper NP, Goedings P, Oesterholt M, Awada A, Desar IM, Lim J, Dean E, Rolfo C, Macpherson I and Banerji U.)
This trial is registered in ClinicalTrials.gov with identifier NCT02277717.