Phase 1 with Expansion Cohorts in a Study of NEO-201 in Adults with Chemo-Resistant Solid Tumors.

TPS2645 Background: NEO-201 is a novel humanized IgG1 monoclonal antibody (mAb) generated against the Hollinshead allogenic colorectal cancer vaccine platform. Briefly, tumor-associated antigens (TAA) derived from tumor membrane fractions pooled from colorectal cancer surgical specimens were screened for delayed-type hypersensitivity and evaluated in clinical trials. The original vaccine was used to generate monoclonal antibodies, one of which is NEO-201. In preclinical data generated in our laboratory, we have demonstrated that NEO-201 exert anti-tumor activity by natural killer (NK)-mediated antibody-dependent cytotoxicity (ADCC) against several tumor type including colorectal and pancreatic cancer models (Fantini, et al. 2018). We have identified NEO-201 antigen as a glycosylated form of CEACAM-5 and -6, which is expressed by tumor tissue but is not present in the surrounding healthy tissue (David, et al. 2018). This could result in a specific anti-tumor activity without significant normal tissue toxicity. Nevertheless, toxicity was further assessed in non-human primates and transient neutropenia was the only adverse event observed. Based on this data we designed a first in human phase I trial to evaluate the safety, maximum-tolerated dose (MTD), pharmacokinetics (PK) and pharmacodynamics (PD) of the humanized monoclonal antibody NEO-201. Methods: This is a first-in-human phase 1 study with expansion cohort to determine the maximum tolerated dose (MTD) and recommended phase II dose (RP2D) of NEO-201 in adults with advanced solid tumors that have high likelihood pof expression NEO201 antigen and have progressed to standard of treatments and have a PS0-2 ECOG. Study design is a classic Fibonacci (3+3) dose escalation, with a cohort expansion at the MTD. NEO-201 is administered intravenously every two weeks, and four different dose levels will be explored (DL1 = 1mg/kg, DL2 = 2mg/kg, DL3 = 4mg/kg and DL4 = 6mg/kg). No intra-patient dose escalation is allowed. Patients will be evaluated for safety every two weeks, with weekly laboratory testing, according to CTCAEv4.0. and with a DLT window of 28 days (cycle 1). Response will be assessed every 8 weeks (2 cycles of treatment) according to RECISTv1.1. Additionally, biological samples will be collected to understand NEO-201 pharmacokinetic, the effect on the immune process and their correlation with treatment toxicity and response. As of February 2019 we have completed enrollment in the first DL and are evaluating for DLT. Clinical trial information: NCT03476681.