In the second half of May several companies reported important progress on their therapeutic ADC products. The Dutch pharmaceutical company Synthon initiated the second phase of the ongoing phase I clinical trial with its investigational anti-HER2 ADC SYD985. During the first part patients with solid tumors of any origin were enrolled. Promising results were obtained in this dose-finding part of the trial in 33 cancer patients who were dosed with between 0.3 and 2.4 mg/kg of SYD985 every three weeks. Very high response rates and durable responses were observed at doses from 1.2 mg/kg onwards in patients whose cancers were refractory to HER2-targeted agents, including Herceptin® and Kadcyla®. The second part will see 48 additional heavily pre-treated patients with HER2-positive breast cancer enrolled into the Phase I trial. This marked a significant next step in the development of SYD985, the frontrunner of the company’s duocarmycin-based ADC platform.
Additionally, Seattle Genetics announced initiation of a pivotal phase III clinical trial, CASCADE, evaluating vadastuximab talirine (SGN-CD33A) in combination with azacitidine (Vidaza) or decitabine (Dacogen) in older patients with newly diagnosed acute myeloid leukemia (AML). SGN-CD33A is an ADC targeting CD33 comprising an engineered cysteine antibody (EC-mAb) stably linked to a pyrrolobenzodiazepine (PBD) dimer. CD33 is expressed on leukemic blasts in nearly all AML patients and expression is generally consistent regardless of age, cytogenetic abnormalities or underlying mutations. Azacitidine and decitabine are hypomethylating agents (HMAs) commonly used in the treatment of older AML patients. The phase III CASCADE study is a randomized, double-blinded, placebo-controlled, global clinical trial. Patients will be randomized on a 1:1 ratio to be treated with an HMA plus SGN-CD33A or an HMA plus placebo. The secondary endpoints include the comparison of composite complete remission rate, event-free and leukemia-free survival, duration of response, safety, and 30- and 60-day mortality rates. This phase III trial will enroll approximately 500 patients globally.