Second-Generation NK Cell Engager Heading to Trial for CD33+ Leukemia
GT Biopharma anticipates initiating the phase 1 clinical trial in the second half of 2024.
The FDA has cleared GT Biopharma’s investigational new drug (IND) application for GTB-5550, a natural killer (NK) cell engager therapy for the potential treatment of with relapsed or refractory (r/r) CD33 expressing hematologic malignancies, including acute myeloid leukemia (AML) and high-risk myelodysplastic syndrome (MDS).The company anticipates initiating the trial in second half of 2024.1
“FDA clearance for GTB-3650 is a tremendous accomplishment and we look forward to submitting our next IND in the first quarter of 2025 for GTB-5550, which will target multiple solid tumors”, Michael Breen, Executive Chairman and Interim Chief Executive Officer, GT Biopharma, said in a statement.1 “As we ramp up our clinical activities, we plan to start the Phase 1 trial with GTB-3650 in the coming months followed by multiple data readouts in 2025. We also expect to start a basket trial with GTB-5550 for multiple solid tumors in 2025 and remain very enthusiastic in our pursuit of additional opportunities for various autoimmune indications where our TriKE’s may have therapeutic utility.”
GTB-3650 is a second generation nanobody NK cell engager(TriKE) therapy. It is a tri-specific molecule composed of a camelid nanobody that binds the CD16 receptor on NK cells, a single chain variable fragment (scFv) that recognizes CD33 on tumor cells, and human IL-15. It followed the company’s first-generation TriKE therapy for the same indications, GTB-3550. 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 human IL-15. GTB-3550 was evaluated in a first-in-human Phase 1 clinical trial in patients with AML and MDS. The therapy was well-tolerated and then discontinued in favor of the second-generation iteration. GT Biopharma previously submitted the IND for GTB-550 in December 2023.2
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“GTB-3650 is designed to target NK cells within the immune system to potentially overcome many of the limitations of current AML chemotherapies,” Breen added.1 “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.”
The phase 1, dose escalation study will enroll up to 6 cohorts of adult patients with r/r CD33+ hematologic malignancies, including AML and high risk MDS. Participants will receive GTB-3650 in 2-week blocks, 2 weeks on and 2 weeks off, for up to 4 months depending on clinical benefit. The trial will primarily be assessing safety and tolerability. Other factors that will be assessed include pharmacokinetics, pharmacodynamics, and in vivo expansion of endogenous patient NK cells and clinical activity.1
“We look forward to advancing GTB-3650 for treatment of CD33+ leukemia. We are excited to expeditiously move this molecule into the clinic as we execute on our clinical objectives in 2024,” Breen said in an earlier statement.2
Other programs in GT Biopharma’s pipeline include GTB-5550, a TriKE targeting B7H3 positive solid tumors, which is currently in IND-enabling studies. In earlier research phases are a PD-L1–targeting TriKE, GTB-4550, and a HER2-targeting TriKE, GTB-6550, both for solid tumor indications.
REFERENCES
1. GT Biopharma announces FDA clearance of investigational new drug (IND) application for GTB-3650, an NK cell engager for treatment of CD33+ leukemia. News release. GT Biopharma. June 27, 2024. https://www.gtbiopharma.com/news-media/press-releases/detail/283/gt-biopharma-announces-fda-clearance-of-investigational-new
2. GT Biopharma announces IND submissionfor GTB-3650 for treatment of CD33+ leukemia. News release. GT Biopharma. December 4, 2023. https://www.gtbiopharma.com/news-media/press-releases/detail/277/gt-biopharma-announces-ind-submission-for-gtb-3650-for
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