Future Directions for NK Cell Platforms in Hematologic Malignancies

Jeffrey Miller, MD, professor of medicine in the Division of Hematology, Oncology, and Transplantation, deputy director of the Masonic Cancer Center, the Roger L. and Lynn C. Headrick Chari in Cancer Therapeutics, and associate scientific director of Molecular and Cellular Therapeutics at the University of Minnesota Medical School, discusses what is next to come following an analysis of GTB-3550.

In a phase 1/2 study (NCT03214666), the safety and efficacy of GTB-3550, a tri-specific killer engager, in high risk hematological malignancies was being evaluated. However, the study was terminated due to the development of GTB-3650.

According to Miller, GTB-3650 is a second-generation TriKE which works by binding to NK cells. The novel molecule is based on camelid single-domain antibody technology and has shown significantly higher potency than GTB-3550 in preclinical models.

Transcription:

0:08 | This second-generation trick nearly binds to NK cells a little bit differently. Binding sequences have the capacity to be from whole antibodies, or single chain of fees, which is, what, GTB-3550 is. We've discovered that if you use a single heavy chain antibody and take that binding sequence, that you can get a camelid binding domain that seems to be tighter, and gives us potency of a drug that is more than 10 to 20 fold better than the GTB-3550 that's currently in the clinic.

1:18 | I think the decision we're trying to make now is how far to go with GTB-3550. I think that at least from the academic perspective, one should go with where their data is. I've been advocating for a plan to continue on with these studies, but then go to the better druggable compound that has better binding activity. I think we're in the process of going through those logistics, obviously talking to the FDA, and trying to weigh all those decisions before we figure if we're going to really go to the initial targeted dose, or whether we're going to try to keep that as proof of concept, and then move on with the better concept that we think will have a better clinical activity.