Byondis investigational breast cancer drug selected for trial

Byondis B.V. (formerly Synthon Biopharmaceuticals) announced that Quantum Leap Healthcare Collaborative (Quantum Leap) selected the company’s investigational antibody-drug conjugate (ADC) SYD985 ([vic-]trastuzumab duocarmazine) for a new investigational treatment arm in its ongoing I-SPY 2 TRIAL for neoadjuvant treatment of locally advanced breast cancer. This treatment arm will focus on treatment for HER2-low early-stage breast cancer.

The I-SPY 2 TRIAL (Investigation of Serial studies to Predict Your Therapeutic Response with Imaging And moLecular analysis) is a standing Phase II randomized, controlled, multicentre study aimed at rapidly screening and identifying promising treatments in specific subgroups of women with newly-diagnosed, high-risk, locally advanced breast cancer (Stage II/III). Quantum Leap, sponsor of the I-SPY 2 TRIAL, leads a pre-competitive consortium that includes the U.S. Food & Drug Administration (FDA), industry, patient advocates, philanthropic sponsors, and clinicians from 16 major U.S. cancer research centres.

The new I-SPY 2 treatment arm will evaluate SYD985 against standard of care therapy in Stage II/III early-stage, high-risk breast cancer patients, with a focus on tumours with heterogeneous and low HER2 expression. Byondis will supply the investigational drug and provide financial and regulatory support. Quantum Leap, as sponsor, will provide the clinical sites and clinical expertise.

SYD985 is Byondis’ most advanced ADC, targeting a range of HER2-positive cancers such as metastatic breast cancer (MBC) and endometrial cancer. The company is currently conducting a Phase III study of SYD985 (TULIP or SYD985.002) to compare its efficacy and safety to physician's choice treatment in patients with HER2-positive unresectable locally advanced or metastatic breast cancer. Previously, the FDA granted fast track designation for SYD985 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).

SYD985 uses Byondis’ unique, proprietary linker-drug (LD) technology. Although marketed ADCs have improved therapeutic indices compared to classical non-targeted chemotherapeutic agents, there is still room for improvement.

SYD985 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 SYD985 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 tumour cell death. SYD985 can be considered a form of targeted chemotherapy.