Background
colorectal cancer, tumor, neutropenia, toxicity, cancer, NEO-201, toxicities, tumors
TUMOR, COLORECTAL CANCER, NEUTROPENIA, CARCINOGENESIS, CANCER, DISEASE, SOLID TUMORS, ADVERSE EFFECT, TUMORS, CYTOTOXICITY
Recent efforts in cancer therapeutics have focused on the development of drugs that activate the immune system against cancer cells to achieve durable disease control. In recent decades, cancer immunotherapies have emerged as promising treatment options for many cancer patients and have increasingly been employed in specific disease settings as either an alternative to traditional chemotherapy and radiotherapy or as adjunctive therapy to these traditional modalities providing additive or even synergistic activity. Most cancer immunotherapies, including immune checkpoint inhibitors, vaccines, and engineered chimeric T-cell receptors, have focused on boosting the adaptive immune system in its activities of immunosurveillance, allowing it to recognize and mount immune responses against tumors [Concurrently with the development of immune checkpoint inhibitors, other mAbs, capable of recognizing tumor-associated antigens and directly eliciting tumor cell killing via antibody-dependent cellular cytotoxicity (ADCC) and/or complement-dependent cytotoxicity (CDC), have been developed [NEO-201 is a humanized IgG1 mAb generated against tumor-associated antigens from patients with colorectal cancer [NEO-201 binding specificity for tumor-associated proteins could be due to the presence of glycan patterns (i.e. O-glycans) attached to the protein carriers during post-translational modifications made during the process of carcinogenesis [The specificity of NEO-201 for a tumor associated antigen suggests a minimal risk of off-target, off-tumor toxicities on surrounding healthy tissue, which has been an important source of toxicity for many mAbs. NEO-201 demonstrated exceptional safety/tolerability in non-human primates, with transient neutropenia, due to high levels of expression of the antigen on mature neutrophils, being the only adverse effect observed [This study reports results from the first-in-human phase I trial designed to determine the MTD and RP2D of NEO-201 in patients with advanced solid tumors which have progressed on or not responded to standard treatments. Additional correlative data are presented related to NEO-201 pharmacokinetics and pharmacodynamics, specifically, for the effects on immune profile and correlation with treatment toxicity and response.