Earlier today, Seattle Genetics confirmed that it discontinued the phase III CASCADE clinical trial of vadastuximab talirine (SGN-CD33A) in frontline older acute myeloid leukemia (AML) patients.

The phase III CASCADE clinical trial is a randomized, double-blind, placebo-controlled study evaluating vadastuximab talirine in combination with the hypomethylating agents (HMAs) azacitidine or decitabine compared to an HMA alone in older patients with newly diagnosed AML. Vadastuximab talirine is a novel investigational ADC targeted to CD33 utilizing Seattle Genetics’ proprietary ADC technology. CD33 is expressed on most AML and MDS blast cells.

Table 1.0: Phase III CASCADE clinical trial of vadastuximab talirine (SGN-CD33A) – NCT02785900.

The company took this action following consultation with the Independent Data Monitoring Committee (IDMC) and after reviewing unblinded data on June 16, 2017.

The data indicated a higher rate of deaths, including fatal infections in the vadastuximab talirine-containing arm versus the control arm of the trial. Based on available data, the safety concerns in this trial do not appear related to hepatotoxicity. Seattle Genetics is suspending patient enrollment and treatment in all of its vadastuximab talirine clinical trials including the ongoing phase I/II clinical trial in frontline high risk myelodysplastic syndrome (MDS).

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Photo 1.0: Clay Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics.

In an announcement today, the company confirmed that it will closely review the data and consult with the U.S. Food and Drug Administration (FDA) to determine future plans for the vadastuximab talirine development program.

“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,” said Clay Siegall, Ph.D., President and Chief Executive Officer at Seattle Genetics.

Ongoing trials
“We are enthusiastic about the many opportunities across our broad pipeline, including brentuximab vedotin (Adcetris®), enfortumab vedotin (ASG-22ME) and SGN-LIV1A. Notably, we are looking forward to reporting data from our ADCETRIS phase III ECHELON-1 trial in frontline Hodgkin lymphoma, and we are on track to advance enfortumab vedotin into a pivotal trial in metastatic urothelial cancer in the second half of 2017 under our collaboration with Astellas,” Siegall concluded.

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