Compass Therapeutics Reveals New CTX-471 Biomarker Data at SITC Annual Meeting

New research has revealed a significant link between the levels of neural cell adhesion molecule (NCAM or CD56) expression and the response and disease control in patients undergoing treatment with CTX-471 monotherapy. An analysis from a Phase 1 monotherapy study showed predictive biomarkers correlated with patient responses and changes in pharmacodynamic markers in those treated with CTX-471, a novel anti-CD137 agonist antibody.

Compass Therapeutics, Inc., a clinical-stage biopharmaceutical company focused on oncology, presented these findings at the Society for Immunotherapy of Cancer (SITC) Annual Meeting. Thomas Schuetz, MD, PhD, CEO of Compass, emphasized the importance of this new data for the clinical strategy of CTX-471. The analysis of tissue and blood samples uncovered a surprising correlation between NCAM (CD56) and patient response to CTX-471, potentially linked to Natural Killer (NK) Cell activation. This finding broadens the development pathway for CTX-471, prompting plans for a Phase 2 monotherapy basket study targeting patients with NCAM-expressing tumors.

The data comes from Compass's Phase 1 open-label, first-in-human study, which evaluated CTX-471 as a monotherapy in patients with metastatic or locally advanced malignancies unresponsive to approved PD-1 or PD-L1 inhibitors. The exploratory data complements previously published safety and efficacy data. The study involved analyzing biopsy specimens and blood samples using multi-parameter immunofluorescence, flow cytometry, and cytokine panels via the Neogenomics Multi-omyx platform. Pharmacodynamic effects were assessed by comparing samples before and after CTX-471 treatment, while response biomarkers were evaluated by comparing baseline samples from patients with varying degrees of tumor response.

The authors propose that NCAM facilitates the response to CTX-471 by enriching activated NK cells expressing CD137 (4-1BB) within the tumor microenvironment. This was specifically observed in NCAM-expressing lymphocytes like NK cells, but not in other lymphocyte subsets such as CD8+ T cells. These findings are novel in a clinical setting and suggest NCAM could be used as a selection marker for future clinical trials.

Key data from the presentation highlighted that CTX-471 causes pharmacodynamic biomarker changes consistent with immune stimulation. Disease control with CTX-471 is associated with measurable baseline biomarkers, and baseline expression of NCAM/CD56 in tumor cells is linked with response and disease control. Additionally, a new baseline circulating cell phenotype was associated with partial responses to CTX-471.

CTX-471 is a fully human monoclonal antibody targeting and activating a novel epitope of the CD137 co-stimulatory receptor, also known as 4-1BB. In preclinical studies, CTX-471 showed potent monotherapy activity against various tumor models and generated long-term functional immunological memory. It is currently being evaluated in a Phase 1b clinical trial for patients with solid tumors that have progressed after treatment with PD-1 or PD-L1 inhibitors. Initial results from the monotherapy cohort included five clinical responses in patients previously treated with checkpoint inhibitors, including a durable partial response in a small-cell lung cancer patient that became a complete response, and four additional partial responses in patients with melanoma and mesothelioma. CTX-471 has generally been well tolerated.

NCAM (CD56) is a membrane glycoprotein involved in neural cell adhesion and central nervous system development, mediating homotypic interactions between cells. In cancer, NCAM is associated with tumor invasion and metastases, particularly in neural crest-derived tumors like metastatic melanoma, small-cell lung cancer (SCLC), and glioblastoma, as well as neuroendocrine tumors (NET). The prevalence of high NCAM expression varies, being present in about 30% of metastatic melanomas and almost all cases of SCLC, glioblastoma, and NETs.

Compass Therapeutics, founded in 2014 and headquartered in Boston, Massachusetts, focuses on developing proprietary antibody-based therapeutics targeting critical biological pathways essential for an effective anti-tumor response. Their approach involves modulating the microvasculature, inducing potent immune responses, and alleviating immunosuppressive mechanisms used by tumors. The company aims to advance its product candidates through clinical development both as standalone treatments and in combination with other therapies.