Seattle Genetics halts trials of latest ADC after safety warning

Seattle Genetics has halted all trials of its vadastuximab talirine after a review uncovered a high death rate in acute myeloid leukaemia patients treated with the drug.

The antibody-drug conjugate (ADC) specialist said it took the action after consulting with an Independent Data Monitoring Committee on the phase 3 CASCADE trial, which reviewed the data on Friday.

The data indicated a higher rate of deaths, including fatal infections in the vadastuximab talirine-containing arm versus the control arm, although liver toxicity was not implicated.

Seattle Genetics, which developed the blood cancer drug Adcetris (brentuximab vedotin) in partnership with Takeda, is suspending patient enrolment and treatment in all trials of the new drug, including an ongoing phase 1/2 trial in frontline high risk myelodysplastic syndrome (MDS).

Things look bleak for vadastuximab talirine after the company said it will review data and consult the FDA to determine future plans for development.

CASCADE was evaluating vadastuximab talirine in combination with hypomethylating agents (HMAs) azacytidine or decitabine, compared with an HMA alone in older patients with new diagnosed AML.

Vadastuximab talirine works by targeting CD33, which is expressed on most AML and MDA blast cells.

Seattle Genetics CEO, Clay Siegall, said: “This is a disappointing and unexpected result for the CASCADE trial. Patient safety is our highest priority, and we will closely review the data and evaluate next steps. AML is a devastating disease with a poor prognosis in most patients, and there is a great need for therapeutics against this disease. We thank the patients, caregivers and investigators for their support of this trial.”

Seattle has a number of other drugs in its pipeline – as well as finding new indications for Adcetris, it has several ADCs including SGN-CD123A in early stage development in relapsed/refractory AML, and enfortumab vedotin, developed in partnership with Astellas in early stage development for metastatic urothelial cancer.