US-based biotechnology company Seattle Genetics has begun a Phase lll clinical trial evaluating vadastuximab talirine (SGN-CD33A; 33A), in combination with azacitidine (Vidaza) or decitabine (Dacogen) in older patients with newly diagnosed acute myeloid leukaemia (AML).
The trail, CASCADE, is a randomised, double-blind, placebo-controlled, global clinical trial.
During the trial, patients will be randomised on a 1:1 ratio to be treated with an hypomethylating agent (HMA) plus 33A or an HMA plus placebo.
Secondary endpoints of the trial include the comparison of composite complete remission rate, event-free and leukaemia-free survival, duration of response, safety, as well as 30-day and 60-day mortality rates.
The trial will enrol around 500 patients across the globe.
Seattle Genetics noted that 33A is an antibody-drug conjugate (ADC) targeted to CD33 using the company's latest technology, comprising an engineered cysteine antibody (EC-mAb) stably linked to a highly potent DNA binding agent called a pyrrolobenzodiazepine (PBD) dimer.
CD33 is expressed on leukemic blasts in almost all AML patients and expression is usually consistent irrespective of age, cytogenetic abnormalities or underlying mutations.
Azacitidine and decitabine are HMAs, which are commonly used to treat older AML patients.
Seattle Genetics president and CEO Clay Siegall said: "Acute myeloid leukemia, or AML, is a devastating disease representing a significant unmet medical need. It impacts approximately 20,000 people in the US each year, with few effective treatment options.
"Older AML patients have a particularly poor prognosis as the majority have high-risk disease characteristics and a median survival of ten months or less with available therapies."
The company stated that data from a Phase l 33A combination trial showed 15 out of 23 evaluable patients achieved complete remission and complete remission with incomplete hematologic recovery (CR / Cri).
At a median follow-up of 7.7 months, median survival is yet to be reached, while 72% of patients remained alive and on study.
Seattle Genetics is additionally assessing 33A across multiple lines of therapy in patients with AML and myelodysplastic syndromes (MDS) in various ongoing trials.
Image: Bone marrow aspirate showing acute myeloid leukemia. Photo: courtesy of VashiDonsk.