Patient deaths end Seattle Genetics leukaemia Phase III trial

Seattle Genetics announced it has discontinued its Phase III Cascade trial of Vadastuximab Talirine (SGN-CD33A) for the treatment of frontline acute myeloid leukaemia (AML), due to patient deaths.

Reviewed data this week indicated a higher rate of deaths, including fatal infections in patients who received the drug.

Seattle said that based on available data, the safety concerns do not appear related to hepatotoxicity, but did not disclose further details.

“This is a disappointment and unexpected result for the Cascade trial,” said CEO Clay Siegall.

“Patient safety is our highest priority, and we will closely review the data and evaluate next steps,” he said.

Following discussions with the Independent Data Monitoring Committee (IDMC), the company has suspended patient enrolment and treatment in all Vadastuximab Talirine trials, including the current trial in frontline high risk myelodysplastic syndrome (MDS).

The FDA halted Phase I studies in December last year following the death of four patients who exhibited signs of liver damage – hepatotoxicity.

The clinical hold was lifted in March this year following an independent review of data from treated patients, and the firm’s agreement to make protocol changes.

Seattle said it will review the data and consult with the US Food and Drug Administration (FDA) to establish future plans for the investigational drug.

Vadastuximab Talirine

Vadastuximab Talirine is an antibody drug conjugate (ADC) that targets cancerous cells via CD33 receptors.

SGN-CD33A is composed of a monoclonal antibody and a DNA binding agent called pyrrolobenzodiazepine (PBD), connected using Seattle’s site-specific conjugation technology, EC-mAb.

The drug has orphan status in Europe and the US for the treatment of acute myeloid leukaemia (AML).