Clinical Trials

Date: 2017-06-19

Type of information: Halting of the trial

phase: 3

Announcement: halting of the trial

Company: Seattle Genetics (USA - WA)

Product: vadastuximab talirine (SGN-CD33A; 33A) combined with either azacitidine or decitabine

Action mechanism:

• antibody drug conjugate/hypomethylating agent. Vadastuximab talirine (SGN-CD33A; 33A) is a novel antibody drug conjugate targeted to CD33 utilizing Seattle Genetics’ newest ADC technology. The CD33 antibody is attached to a highly potent DNA binding agent, a pyrrolobenzodiazepine (PBD) dimer, via a proprietary site-specific conjugation technology to a monoclonal antibody with engineered cysteines (EC-mAb). PBD dimers are significantly more potent than systemic chemotherapeutic drugs and the site-specific conjugation technology (EC-mAb) allows uniform drug-loading of the cell-killing PBD agent to the anti-CD33 antibody. The antibody drug conjugate is designed to be stable in the bloodstream and to release its potent DNA binding agent upon internalization into CD33-expressing cells.
• Azacitidine and decitabine are hypomethylating agents (HMAs) commonly used in the treatment of older AML patients.

Disease: acute myeloid leukemia

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• The phase 3 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 acute myeloid leukemia .(NCT02785900)

Latest news:

• • On June 19, 2017, Seattle Genetics announced that it is discontinuing the phase 3 CASCADE clinical trial of vadastuximab talirine (SGN-CD33A) in frontline older acute myeloid leukemia (AML) patients.
• Seattle Genetics 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 1/2 clinical trial in frontline high risk myelodysplastic syndrome (MDS). Seattle Genetics will closely review the data and consult with the FDA to determine future plans for the vadastuximab talirine development program.
• • On May 25, 2016, Seattle Genetics announced initiation of a pivotal phase 3 clinical trial, called CASCADE, evaluating vadastuximab talirine (SGN-CD33A; 33A) in combination with azacitidine (Vidaza®) or decitabine (Dacogen®) in older patients with newly diagnosed acute myeloid leukemia (AML).  The phase 3 CASCADE study is designed to evaluate if vadastuximab talirine in combination with azacitidine or decitabine can extend overall survival compared to azacitidine or decitabine alone in older patients with newly diagnosed AML. Patients will be randomized on a 1:1 ratio to be treated with an HMA plus vadastuximab talirine or an HMA plus placebo. The secondary endpoints include the comparison of composite complete remission rate (complete remission and complete remission with incomplete hematologic recovery; CR/CRi), event-free and leukemia-free survival, duration of response, safety, and 30- and 60-day mortality rates. The phase 3 trial will enroll approximately 500 patients globally.

Is general: Yes