Compass Therapeutics announced new biomarker data for CTX-471, an anti-CD137 agonist antibody, at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. The Phase 1 trial results indicate a significant correlation between neural cell adhesion molecule (NCAM/CD56) expression and patient response to CTX-471 monotherapy in advanced malignancies that had progressed on PD-1/PD-L1 inhibitors. This finding suggests NCAM could serve as a predictive biomarker for patient selection in future clinical trials, potentially improving the drug's efficacy profile.
NCAM as a Predictive Biomarker
The study revealed that tumor cell NCAM appears to enrich activated natural killer (NK) cells in the tumor microenvironment. These NK cells express the CTX-471 target, CD137 (4-1BB). This novel mechanism suggests that NCAM expression could be used to identify patients most likely to benefit from CTX-471 treatment. According to Thomas Schuetz, MD, PhD, CEO of Compass, this discovery is "extremely important for CTX-471 and our clinical strategy," potentially expanding the drug's development pathway.
Clinical Trial Data and Pharmacodynamic Effects
The data comes from an open-label, first-in-human Phase 1 study evaluating CTX-471 as a monotherapy in patients with metastatic or locally advanced malignancies who had progressed while receiving an approved PD-1 or PD-L1 inhibitor. The analysis of biopsy specimens and blood samples showed that CTX-471 pharmacodynamic biomarker changes were consistent with immune stimulation. Furthermore, baseline tumor cell expression of NCAM/CD56 was associated with response and disease control.
Future Development Plans
Compass Therapeutics is now planning a Phase 2 monotherapy basket study of CTX-471 in patients whose tumors express NCAM. This patient population represents a significant unmet medical need, particularly those who have progressed on PD-1/PD-L1 inhibitors. The company believes that this targeted approach could accelerate CTX-471's path to market.
About CTX-471
CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB. Preclinical studies have demonstrated potent monotherapy activity against multiple syngeneic tumor models. The antibody is currently being evaluated in a Phase 1b clinical trial in patients with solid tumors that have progressed after at least three months on an approved PD-1 or PD-L1 inhibitor. Initial results from the monotherapy cohort included clinical responses in patients who previously received checkpoint inhibitors, including a durable complete response in a patient with small-cell lung cancer and additional partial responses in patients with melanoma and mesothelioma.
