GTB-3550 Shows Early Efficacy as MDS and AML Therapy

GTB-3550 TriKE had demonstrated early clinical promise as a monotherapy for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed (R/R) acute myeloid leukemia (AML), according to a press release by GT Biopharma, Inc.

GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composted of heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of interleukin 15 (IL-15). GTB-3550 activates natual killer (NK) cells through the IL-15 portion of the molecule. This self-sustaining signal not only activates NK cells but also enhances their ability to kill. The agent is also intended to be studied in other CD33-positive hematopoietic malignancies in addition to MDS and AML.

Interim results of a recent phase 1/2 clinical trial (NCT03214666) found that patients treated with GTB-3550 had up to a 63.7% reduction in bone marrow blast levels, resulting in clinical benefit. Endogenous NK cell function, proliferation, and immune surveillance. No cytokine release syndrome was observed, and no progenitor-derived or autologous/allogenic cell therapy was required.

The single-center, interventional, non-randomized sequential assignment trial, has an estimated enrollment of 60 participants and an estimated study competition date of August 2025. The primary outcome of phase 1 is maximum tolerated dose (MTD). The primary outcome of phase 2 portion of the study is incidence of complete and partial remission due to the experimental treatment. Secondary outcomes included rate of treatment-related adverse events (TRAE) and overall survival (OS).

In phase 1, patients received a single course of GTB-3550 at 1 of 6 assigned dose levels as 3 weekly treatment blocks. During the block, 4 consecutive 24-hour continuous infusions were followed by a 72-hour break after block 1 and 2. All treatment was given as impatient treatment. Assigned dose was calculated based on weight within 5 days to or on the day of the 1st dose. Dose cannot be recalculated. The 6 dose levels were, 5 μg/kg/day, 10 μg/kg/day, 25 μg/kg/day, 50 μg/kg/day, 100 μg/kg/day, and 200 μg/kg/day.

In phase 2, the treatment schedule was the same as it was in phase 1. During this phase, patients received the MTD.

In order to participate, patients must be between 18 and 75 years old, have adequate organ function, and must have MDS or AML with no good standard of care treatment options. Patients with new or progressive pulmonary infiltrates, uncontrolled bacterial, fungal, or viral infections, active hepatitis B or hepatitis C virus, or a history of central nervous system malignancy or symptoms of active CNS disease are not eligible to participate. 

"We believe GTB-3550 TriKE™ sets a new standard for NK cell engager therapies due to the incorporation of Interleukin 15 (IL-15) directly in the protein backbone. The flexibility and versatility of our TriKE™ platform allows us to change the cancer cell targeting moiety of TriKE™ to attack different cancers while maintaining the core NK cell activation, proliferation and persistence attributes of the molecule," said Anthony J. Cataldo, GT Biopharma's chairman and chief executive, in a press release. "The TriKE™ is a true monotherapy, unlike all other NK cell technologies in development. The novel TriKE™ uniquely does not need any outside NK cell manufacturing or combination drugs, to supplement or assist. Further, the TriKE™ does not require pre-conditioning of the patient's immune system. These supplemental requirements of competitive technologies add tremendous cost to an already costly therapeutic approach. Everything the TriKE™ does happens with no outside assistance whatsoever. We believe the TriKE's clinical data is demonstrating exactly that, opening the door to a significantly more cost-effective off-the-shelf therapeutic."

Other interim results showed that in addition to the reduction in bone marrow blasts levels, GTB-3550 help the exhausted or non-functional endogenous NK cell population and direct the killing of AML and MDS cancer cells. This was achieved without the need the co-administration addition of supplemental progenitor-derived or autologous/allogenic engineered NK cells.

_REFERENCE:

_{GT Biopharma announces GTB-3550 TriKE monotherapy rescues and restores NK cell immune surveillance in relapsed/refractory AML and MDS cancer patients. News Release. GT Biopharma, Inc. April 12, 2021. Accessed April 13, 2021. https://bit.ly/3aanflR.}