A Phase 1b study testing Mylotarg (gemtuzumab ozogamicin) plus Venclexta (venetoclax) for adults with relapsing or refractory acute myeloid leukemia (AML) is currently enrolling patients.
The trial (NCT04070768) is taking place across four clinical sites in the U.S., led by the University of Illinois Cancer Center in Chicago. The other sites are the Indiana University Melvin and Bren Simon Comprehensive Cancer Center, the University of Michigan Health System, and the University of Nebraska Medical Center. More information on contacts and locations can be found here.
AML patients ages 18 to 75, with relapsing or resistant cancers, are being recruited. The participants must have failed to respond to treatment or have had their disease progress despite therapy — no more than three prior treatments — and have at least 20% of cancer cells positive for the CD33 protein.
Five of the target 24 participants have already been enrolled. Patient recruitment is expected to be completed by April 2021.
Mylotarg, developed by Pfizer subsidiary Wyeth Pharmaceuticals, belongs to a class of therapies known as antibody-drug conjugates. These therapies are composed of an antibody that targets a specific cancer protein and is attached to a toxic compound that kills cancer cells.
In the case of Mylotarg, the antibody targets the CD33 protein, which is present in 90% of AML cells. Once bound to the protein, Mylotarg releases its toxic payload into the cell, triggering the cell’s death (apoptosis) without harming healthy cells.
The combination of Mylotarg plus Venclexta, which makes cells cancer cells more vulnerable to death, is expected to boost patients’ responses. Venclexta was developed by AbbVie and Genentech.
“As Gemtuzumab kills leukemia cells through inducing a form of cell death called apoptosis, and Venetoclax primes cancer cells to undergo apoptosis, the synergy of the combination should prove effective in patients with leukemia,” John Quigley, MD, associate professor of hematology and oncology at the University of Illinois College of Medicine and the trial’s lead investigator, said in a press release.
The first group of three participants will be assigned to one cycle of the low dose of the combo therapy. If these patients show no dose-limiting toxicities, three additional participants will be given Mylotarg plus a higher dose of Venclexta. The dosing will continue until the maximum tolerated dose of Venclexta is reached, or the level at which less than 33% of participants experience a dose-limiting toxicity.
In addition to assessing the combination therapy’s maximum tolerated dose, the trial will evaluate its efficacy, including patients’ overall response rate — or the proportion of participants who have a partial or complete response to therapy — and overall survival.
Mylotarg was recently approved by the U.S. Food and Drug Administration as a first-line treatment for children, ages one month or older, who have AML positive for the CD33 protein. The therapy already had been approved for adults with newly diagnosed AML, and for adults and children ages 2 or older with relapsed or refractory AML.