Synthon starts second part of phase I trial with anti-HER2 antibody-drug conjugate SYD985

The second part will see 48 additional heavily pre-treated patients with HER2-positive breast cancer enrolled into the SYD985.001 trial. This marks an important next step in the development of SYD985, the frontrunner of Synthon’s duocarmycin-based ADC platform.

Promising results were obtained in the dose-finding part of the Phase I trial in 33 cancer patients who were dosed with between 0.3 and 2.4 mg/kg of SYD985 every three weeks. Most noticeably, very high response rates and durable responses were observed in patients whose cancers were refractory to HER2-targeted agents, including trastuzumab (Herceptin) and trastuzumab emtansine (Kadcyla), following treatment with SYD985 at doses from 1.2 mg/kg onwards.

Although data from the dose-finding part – which includes patients with solid tumors of any origin – will continue to be collected, evaluation of the larger cohort of 48 heavily pre-treated breast cancer patients with HER2-positive tumors (i.e. HER2 3+ or FISH-positive) has been initiated.

Clinical evaluation in this heavily pre-treated patient population, whose cancers are refractory to multiple lines of registered HER2-targeting treatments including Herceptin® and Kadcyla®, will continue to collect data on efficacy, safety and tolerability of SYD985 treatment at a starting dose of 1.2 mg/kg.

Data from this cohort will enable Synthon to design the first pivotal trial with SYD985 as suggested by several national regulatory authorities and subject to an ongoing EMA scientific advice request regarding the most optimal development pathway.

Synthon will shortly submit a pre-IND (Investigational New Drug Application) meeting request to the U.S. FDA addressing the same topic, with the aim of extending this clinical development program to include U.S. clinical sites under an IND.

"The auspicious data we have already obtained with SYD985 confirms our belief in this potential new HER2-targeting treatment for patients whose cancers have become refractory to currently available anti-HER2-treatments," said Jacques Lemmens, founder and CEO of Synthon.

He continued: "Encouraged by the enthusiasm of our principal investigators and the regulatory bodies that have been consulted, we are further expediting our efforts to drive this compound forward towards a market authorization. The expanded cohort will provide us with information about the minimum effective dose; a very important parameter in this vulnerable group of patients."

Meanwhile, the evaluation in the dose-finding part of the trial continues to further investigate efficacy and safety of repeated treatment cycles.

After determination of the recommended dose later this year, more patients will be enrolled in this trial, including those with breast cancer with lower HER2 expression (HER2 1+/2+ or FISH-negative) as well as those with gastric, endometrial or bladder cancer.