Date: 2014-04-02
Type of information:
phase: preclinical
Announcement: results
Company: Synthon (The Netherlands)
Product: SYD985 (HER2-targeting antibody-drug conjugate based on trastuzumab and Synthon’s proprietary cleavable linker-duocarmycin (vc-seco-DUBA) payload)
Action mechanism: SYD985 is an HER2-targeting antibody-drug conjugate (ADC).
Disease: breast cancer
Therapeutic area: Cancer - Oncology
Country:
Trial details:
Latest
news: * On April 2, 2014, Synthon Biopharmaceuticals has announced the results of a head-to-head comparative program of its antibody-drug conjugate (ADC) SYD985 with Roche’s market leading anti-HER2 ADC, T-DM1 ( Kadcyla®). Comparisons were drawn in in vitro and in vivo testing. In the study, which involved breast cancer models, SYD985 demonstrated unprecedented anti-tumor activity and clearly outperformed T-DM1, particularly where there was a low expression of HER2. In vivo anti-tumor activity was assessed in a series of tumor cell line and patient-derived breast-cancer xenograft models with varying HER2 expression levels, including HER2 3+, HER2 2+ and HER2 1+ models. Both SYD985 and T-DM1 showed anti-tumor activity in the HER2 3+ models, although SYD985 was slightly more active. SYD985 demonstrated very potent anti-tumor activity in the FISH-negative models that were either HER2 2+ or HER2 1+, contrary to T-DM1 which was completely inactive. In these low expressing HER2 tumor models, SYD985 was even able to induce complete tumor remission after a single dose of 3 mg/kg.In vitro, SYD985 and T-DM1 were studied in a panel of eight cell lines expressing different levels of HER2. In cell lines with high HER2 expression (characterized as HER2 3+), both SYD985 and T-DM1 showed similar potencies. However, in cell lines with low HER2 expression (characterized as HER2 1+ and 2+), SYD985 was substantially more potent than T-DM1. More in-depth analyses and preclinical data on this benchmark study with SYD985 will be presented at the AACR Annual Meeting 2014.Based on these findings, the preclinical profile of SYD985 may enable the extension of the target population of cancer patients who may respond to this treatment to include FISH-negative / IHC-HER2 1+ and 2+ patients. Analogous to T-DM1, SYD985 will be tested in refractory breast cancer patients who are FISH-positive and/or IHC-HER2 3+, but these recent data also warrant clinical studies with SYD985 in patients with HER2 1+ and 2+ malignancies. Synthon is preparing for the ‘first-in-human study which is planned to start in the second half of 2014. The company believes this Phase I clinical trial will further validate its ADC technology as potentially best-in-class.
