Crossbow Therapeutics Doses First Patient in Phase 1 Trial of First-in-Class T-Cell Engager CBX-663
核心洞察
Crossbow Therapeutics (搜索) has dosed the first participant in the TelOscope-001 Phase 1 trial of CBX-663 (搜索), a first-in-class T-cell engager for multiple hematologic and solid tumors.
The open-label, dose-escalation study will assess safety, tolerability, and clinical activity in patients with relapsed or refractory myeloid malignancies (搜索), advanced solid tumors, and recurrent or progressive glioblastoma multiforme (搜索).
CBX-663 (搜索) is a bispecific antibody targeting telomerase reverse transcriptase (搜索) (TERT), a protein overexpressed in approximately 90% of all cancers, via TERT-derived pHLA complexes.
Crossbow Therapeutics (搜索), Inc. has dosed the first participant in its TelOscope-001 Phase 1 clinical trial of CBX-663 (搜索), a first-in-class T-cell engager (TCE) being developed for the treatment of multiple hematologic and solid tumors. The first-in-human study represents the clinical debut of a novel approach that targets peptide human leukocyte antigen (pHLA) complexes on tumor cells using antibodies that mimic T-cell receptors (TCR-mimetics).
CBX-663 (搜索) is the second candidate developed through Crossbow's T-Bolt™ platform, a portfolio of novel TCE molecules. The wholly owned candidate is a potent bispecific antibody that targets telomerase reverse transcriptase (搜索) (TERT), a protein that drives tumor growth and is overexpressed in approximately 90% of all cancers.
"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," said Briggs Morrison, M.D., Chief Executive Officer of Crossbow Therapeutics (搜索). "CBX-663 (搜索) 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."
Mechanism of Action
CBX-663 (搜索) binds to TERT-derived pHLA complexes on the surface of tumor cells and activates T cells through a CD3-binding arm, one half of an engineered bispecific antibody designed to grab onto the CD3 protein on T cells. The molecule includes two binding domains for TERT, which increase its ability to engage tumor cells and boost immune activation.
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's T-Bolt™ platform combines optimized antibody libraries with precision screening to identify high-affinity, highly specific binders to intracellular tumor antigens presented on cancer cells as pHLA complexes.
Trial Design
The Phase 1, open-label, dose-escalation TelOscope-001 study is evaluating the safety, tolerability, and clinical activity of CBX-663 (搜索) in patients with relapsed or refractory myeloid malignancies (搜索), advanced solid tumors, or recurrent or progressive glioblastoma multiforme (搜索) (GBM). 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.
Preclinical Evidence
In preclinical studies, CBX-663 (搜索) drove potent, antigen-specific tumor killing across multiple TERT-positive cancer models, with minimal activity against TERT-negative or HLA-mismatched cells. The candidate also demonstrated a favorable safety profile and pharmacokinetics comparable to conventional antibody therapies.
Crossbow designed and is conducting the TelOscope-001 clinical 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.