Phase 1 GTB-3650 Trial Advances for CD33+ Malignancies
Cohort 1 of the GTB-3650 phase 1 trial completed with no safety issues observed in patients with CD33-expressing hematologic malignancies.
A close-up of a red cell with a red blood cell in the backgroundI: © Bipul Kumar - stock.adobe.com
Cohort 1 of the phase 1 dose-escalation trial (NCT06594445) studying GTB-3650, a second-generation TriKE, for the treatment of patients with relapsed/refractory (R/R) CD33-expressing hematologic malignancies has successfully been completed.1 With this, the dosing in cohort 2 of the trial may begin.
The formal safety review of cohort 1 showed there to be no safety or tolerability issues observed. In this cohort, patients also demonstrated early evidence of increased immunologic activity, according to multiple assays of various blood biomarkers. These findings support GTB-3650’s ability to activate endogenous natural killer (NK) cells and induce NK cell expansion.
The study may now move forward with cohort 2. More detailed results from the phase 1 portion of the study are expected to be released later in 2025 after additional dose cohorts have been completed.
Currently, GTB-3650 is being evaluated for the treatment of R/R CD33-expressing hematologic malignancies. All patients in cohort 1 have now undergone the first and second dosing cycles, and the first patient in cohort 2 of the study has now been treated with the first dose cycle.
The study plans to include patients with an absolute lymphocyte count ≥ 200 cells/µL or absolute circulating CD56+/CD3– NK cell count >25 cells/µL within the 14 days prior to cycle 1 day 1, peripheral blasts ≤20,000 at the time of treatment start, and adequate organ function within 14 days of day 1 of the first cycle.2 For just the dose-finding component, patients are required to agree to stay within a 60-minute drive of the study center through the day 29 visit of cycle 1, which also makes up the end of the dose-limiting toxicity period.
The trial is assessing GTB-3650 in up to around 14 patients who will make up 7 cohorts. Here, GTB-3650 is being given to patients in 2-week blocks where it will be administered 2 weeks on and 2 weeks off for up to 4 months based on clinical benefit.
The study’s primary end point is to determine the maximum tolerated dose of GTB-3650. Secondary end points are to evaluate the safety and feasibility of the agent based on the incidence of adverse events, event-free survival, and overall survival. The study will also assesspharmacokinetics, pharmacodynamics, in vivo expansion of endogenous patient NK cells, and clinical activity.1
In December 2023, the FDA received an investigational new drug (IND) application for the development of GTB-3650 for patients with CD33-positive leukemia, including R/R acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome.3 The FDA cleared the IND application in June 2024.
“GTB-3650 is designed to target NK cells within the immune system to potentially overcome many of the limitations of current AML chemotherapies,” said Michael Breen, executive chairman and interim chief executive officer of GT Biopharma, in a press release.4 “Our trial design should give us an early read on safety and potential therapeutic activity and also provide valuable learnings that we can translate into our clinical development plans for follow-on TriKE molecules, including GTB-5550.”
