GT Biopharma has successfully advanced its Phase 1 dose-escalation trial of GTB-3650 to the second patient cohort following promising results from initial human dosing. The clinical-stage immuno-oncology company reported no safety or tolerability issues in the first cohort, with early evidence of immune activation supporting the therapy's mechanism of action.
GTB-3650, a second-generation Tri-specific Killer Engager (TriKE) immunotherapy, is being evaluated for the treatment of relapsed or refractory CD33-expressing hematologic malignancies. The therapy represents a novel approach to cancer treatment by specifically activating and expanding a patient's natural killer (NK) cells to enhance immune-mediated destruction of cancer cells.
Trial Design and Progress
The Phase 1 study is expected to enroll approximately 14 patients across seven dose cohorts. GTB-3650 is administered in two-week cycles – two weeks on treatment followed by two weeks off – for up to four months, depending on clinical response.
Following a formal safety review of Cohort 1, where patients completed their first and second dosing cycles, the company received clearance to proceed with Cohort 2. The first patient in this second cohort has already received their initial dose.
"The successful completion of Cohort 1 with no safety or tolerability issues is an important milestone for our GTB-3650 program," said a company representative. "We're particularly encouraged by the early biological signals we're seeing in these patients."
Promising Biological Signals
Both patients in the first cohort showed early evidence of increased immunologic activity based on multiple assays of various blood biomarkers. These findings support GTB-3650's ability to activate endogenous NK cells and induce NK cell expansion – key mechanisms by which the therapy is designed to work.
The trial is comprehensively evaluating several parameters, including:
- Safety and tolerability across multiple dose levels
- Pharmacokinetics and pharmacodynamics
- In vivo expansion of endogenous patient NK cells
- Preliminary signs of clinical efficacy
GT Biopharma plans to release more detailed Phase 1 data later in 2025 upon completion of additional dosing cohorts.
The TriKE Platform Technology
The TriKE platform represents a novel approach to cancer immunotherapy. Unlike conventional treatments, TriKE molecules are designed to bridge NK cells to cancer cells, facilitating targeted immune attack. The technology holds potential advantages over other immunotherapies:
- Direct activation of NK cells without the need for additional cytokine support
- Enhanced specificity for cancer cells expressing the target antigen (CD33)
- Potential for reduced off-target effects compared to some other immunotherapies
GT Biopharma holds an exclusive worldwide license agreement with the University of Minnesota to develop and commercialize therapies using TriKE technology. The company's pipeline focuses on both hematologic malignancies and solid tumors using this NK cell-based approach.
Market and Company Impact
Following the announcement, GT Biopharma's stock (NASDAQ: GTBP) saw an 11.13 percent increase, trading at $2.47. The positive market response reflects investor confidence in the company's progress with its lead clinical program.
The company continues to advance its broader TriKE platform, targeting difficult-to-treat hematologic and solid tumors. This approach represents part of a growing interest in NK cell-based immunotherapies as alternatives or complements to T-cell focused approaches like CAR-T therapy.
For patients with relapsed or refractory CD33-expressing hematologic malignancies, who often have limited treatment options, the development of GTB-3650 could potentially provide a new therapeutic avenue if later-stage trials continue to show promising results.
More information about the trial can be found on clinicaltrials.gov with the identifier: NCT06594445.
