Crossbow Therapeutics has dosed the first patient in the TelOscope-001 Phase 1 clinical trial of CBX-663, a first-in-class T-cell engager being developed for multiple hematologic and solid tumors.
The first-in-human study is evaluating CBX-663 in patients with relapsed or refractory myeloid malignancies, advanced solid tumors, and recurrent or progressive glioblastoma multiforme.
CBX-663 is the second candidate developed through Crossbow’s T-Bolt platform, a portfolio of T-cell engager molecules designed to target peptide human leukocyte antigen complexes on tumor cells using antibodies that mimic T-cell receptors.
The wholly owned candidate is a bispecific antibody targeting telomerase reverse transcriptase, or TERT, a protein involved in tumor growth that Crossbow said is overexpressed in approximately 90% of cancers.
TERT enables cancer cells to bypass normal cellular aging mechanisms and continue proliferating, making it an attractive target for oncology drug development.
CBX-663 is designed to recognize a TERT-derived pHLA complex displayed on the surface of tumor cells while simultaneously activating T cells through a CD3-binding arm.
The molecule also includes two TERT-binding domains, which Crossbow designed to strengthen its interaction with tumor cells and increase immune activation.
The Phase 1 TelOscope-001 study is an open-label, dose-escalation trial assessing the safety, tolerability and clinical activity of CBX-663.
Crossbow is administering the candidate using a fixed step-up dosing schedule as it evaluates dose levels and monitors patients for safety and early signs of antitumor activity.
In preclinical studies, CBX-663 produced potent, antigen-specific tumor killing across multiple TERT-positive cancer models, while showing minimal activity against TERT-negative or HLA-mismatched cells.
The candidate also demonstrated what the company described as a favorable preclinical safety profile and pharmacokinetic characteristics comparable with conventional antibody therapies.
Crossbow developed CBX-663 using its proprietary T-Bolt platform, which combines optimized antibody libraries with precision screening to identify high-affinity and highly specific binders to intracellular tumor antigens presented on cancer cells as pHLA complexes.
This approach is intended to extend antibody-based therapies beyond targets located directly on the surface of cancer cells by allowing antibodies to recognize fragments of intracellular proteins displayed through the HLA system.
Crossbow designed and is conducting the TelOscope-001 study and expects to report initial clinical data around the end of 2027.
The trial represents an important step in the company’s effort to validate its TCR-mimetic antibody platform in humans and determine whether targeting TERT-derived complexes can provide a therapeutic approach across multiple cancer types.
KEY QUOTE:
“TERT is a priority target for anticancer therapy due to its widespread overexpression, which allows cancer cells to bypass cellular aging, promotes uncontrolled tumor proliferation, and correlates with disease severity. CBX-663 selectively targets a TERT-derived pHLA complex expressed across a broad range of hematologic and solid malignancies, making it a promising therapeutic candidate in an area of heightened unmet medical need.”
Briggs Morrison, M.D., Chief Executive Officer of Crossbow Therapeutics
