Clinical stage immuno-oncology innovator GT Biopharma, Inc. (NASDAQ: GTBP) is targeting multiple hematologic and solid tumor cancers with its first-in-class NK cell engager protein biologic technology platform: TriKE™. TriKE™ is designed to rescue the patient’s native natural killer cell (NK cell) population. Additionally, TriKE™ has the unique ability to be a self-sustaining,
self-activating, target-directed NK cell therapeutic agent – resulting in a persistent, 24/7 serial cancer cell killer, lasting for 60-90 days – without the need to transplant NK cells in patients or be co-administered with other therapeutic agents. For these reasons, GT Biopharma’s novel TriKE™ therapy will be significantly less expensive than other cancer treatments, opening the door to an off-the-shelf therapeutic for patients.
GT Biopharma recently reported updated interim Phase I/II clinical trial results for its lead therapeutic candidate, GTB-3550 TriKE™. GTB-3550 is currently being evaluated for the treatment of high-risk myelodysplastic syndromes (MDS) and refractory/relapsed acute myeloid leukemia (AML). Highlights of the results include:
- Up to 63.7% Reduction in Bone Marrow Blast Levels
- Restores Patient’s Endogenous NK Cell Function, Proliferation and Immune Surveillance
- No Progenitor-derived or Autologous/Allogenic Cell Therapy Required
- No Cytokine Release Syndrome (CRS) Observed
- Three out of the last five patients treated (25mcg/kg/day to 100 mcg/kg/day) responded
Before therapy, data shows all patients’ endogenous (native) NK cells are exhausted and no longer functioning. Their native NK cells have lost the ability to kill cancer cells. To date, nine patients have been treated in the escalating-dose part of the Phase I/II Expansion clinical trial.
Of particular note, GTB-3550 TriKE™ is currently being administered to patients at doses significantly higher than the reported MTD (Maximum Tolerated Dose) for continuous infusion of recombinant human IL-15 (Interleukin-15), (Waldmann, TA et al, Clin Cancer Res. (2019)
25:4945–54). IL-15 is one of the most potent and, therefore, potentially dangerous, cytokines for killing cancer. GTB-3550 is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies, and a modified form of IL-15. The NK cell stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill.
In the ongoing trial, Patients 5-9 were treated with increasing doses of GTB-3550 (25mcg/kg/day, 50mcg/kg/day and 100mcg/kg/day, respectively). Three of the five patients (60%) experienced reduction in bone marrow blasts with two patients (one patient treated at the 50mcg/kg/day dose level and one patient treated at the 100mcg/kg/day dose level) experiencing significant reductions in bone marrow blast levels. As previously reported, Patient 7 treated at the 50mcg/kg/day dose level achieved a 61.7% reduction in bone marrow blast levels from 12% before therapy to 4.6% after GTB-3550 therapy. Patient 9 treated at the 100mcg/kg/day dose level achieved a 63.7% reduction in bone marrow blast levels from 22% before therapy to 8% after therapy. All patients treated at these higher doses of GTB-3550 did not experience any Grade of CRS.
In addition to its well tolerated safety profile, GTB-3550 therapy is showing promising clinical efficacy – notably significant reduction in bone marrow blast levels, improved NK cell function, proliferation and persistence. Correlative studies have shown reproducible endogenous NK cell activity in all patients. NK cell activation increases early during treatment. This finding correlated with an increase proportion and absolute number of NK cells occurring during treatment. Targeted delivery of IL-15 to NK cells via GTB-3550 TriKE™ showed preferential proliferation of NK cells and significantly less effect on CD8+ and CD4+ T-cells. Enhanced AML and MDS target cell killing was observed, while there was no observed CD16 shedding by patients’ NK cells. This data indicates GTB-3550 TriKE™ rescues the patient’s exhausted/inhibited endogenous NK cells, resulting in their activation, target-directed killing, proliferation and persistence.
“We are pleased with the continued clinical performance of our lead GTB-3550 TriKE™ product candidate as we continue dose escalation,” said Anthony J. Cataldo, GT Biopharma’s Chairman and CEO. “This early data indicates GTB-3550 therapy demonstrates significant bone marrow blast level reductions in AML and MDS patients without the need for expensive progenitor-derived or autologous/allogenic cell therapies. We believe as we continue to dose escalate GTB-3550 TriKE™, more patients will experience greater clinical efficacy. The ability of TriKE™ to be effective in the patient without the addition of outside supplemental engineered NK cells or the need for any combination drugs, sets TriKE™ apart from other cancer therapies. This is also the reason why TriKE™ therapy will be significantly less expensive than other treatments, opening the door to an off-the-shelf therapeutic.”
The ongoing, first-in-human GTB-3550 TriKE™ Phase I/II clinical trial is increasing the understanding of how TriKE™ operates in the human body. Two leading solid tumor TriKE™ candidates – GTB-4550, for PD-L1-positive cancers, and GTB-5550, for B7H3-positive cancers – have progressed to GMP manufacturing at Oklahoma City-based Cytovance Biologics, GT Biopharma’s manufacturing partner.
GT Biopharma’s novel, first-in-class GTB-3550 TriKE™ Phase I/II clinical trial will proceed to the next cohort, dosed at 200 mcg/kg/day, after Patient 10 dosing concludes. GTB-3550 TriKE™ is a single-chain, tri-specific scFv recombinant fusion protein conjugate composed of the variable regions of the heavy and light chains of anti-CD16 and anti-CD33 antibodies and a modified form of IL-15. The NK cell stimulating cytokine human IL-15 portion of the molecule provides a self-sustaining signal that activates NK cells and enhances their ability to kill. Dr. Jeffrey S. Miller, Professor of Medicine at the University of Minnesota and GT Biopharma’s Consulting Chief Medical Officer, and his colleagues developed TriKE™. GT Biopharma has an exclusive worldwide license with the University of Minnesota to further develop and commercialize therapies using TriKE™ technology.
GT Biopharma, Inc. (NASDAQ: GTBP) is a clinical stage biopharmaceutical company focused on the development and commercialization of immuno-oncology therapeutic products based on our proprietary TriKE™ NK cell engager platform. Our TriKE™ platform is designed to harness and enhance the cancer killing abilities of a patient’s immune system natural killer cells (NK cells). GT Biopharma has an exclusive worldwide license agreement with the University of Minnesota to further develop and commercialize therapies using TriKE™ technology. For more information, please visit gtbiopharma.com.