NEO-102, an Anti-MUC5AC Monoclonal Antibody, in Chemotherapy-Refractory Metastatic Colorectal Cancer

NEO-102 (NPC-1C, ensituximab) is a novel chimeric IgG1 monoclonal antibody targeting a variant of MUC5AC that is specific to colorectal cancer (CRC). Its mechanism of action is through antibody-dependent cellular cytotoxicity (ADCC). An earlier, phase 1 study established the maximum tolerated dose at 3.0 mg/kg intravenously every 2 weeks with encouraging early signs of clinical activity.1 Kim and colleagues reported initial results of the subsequent phase 2 study, which was a single-arm, open-label, multicenter clinical trial of NEO-102 in patients with metastatic CRC (mCRC) who had failed at least 2 lines of standard chemotherapy.2 An immunohistochemistry-based companion diagnostic assay was used to select eligible patients whose tumors expressed the target in >20% of tumor cells.

NEO-102 at 3.0 mg/kg intravenously was administered every 2 weeks in patients with metastatic, locally advanced, unresectable, or recurrent CRC until disease progression or dose-limiting toxicity. The primary end point was overall survival (OS). Secondary study objectives were to evaluate response rate as measured by RECIST criteria and analyze patient peripheral blood mononuclear cells for ADCC and immune cytokine profiling.

A total of 48 patients enrolled were evaluable, and 15 (31%) of 47 patients remained alive as of December 2015 with an ongoing median OS of 6.8 months (range, 1.8-25+ months). Of these heavily pretreated patients, 37 were evaluable for response: 18 (49%) demonstrated stable disease by RECIST. Grade 3/4 adverse events were anemia (1.3%), hyperbilirubinemia (0.9%), diarrhea (0.4%), fatigue (0.9%), and headache, nausea, and vomiting (all 0.4%). Correlative studies of the effect of NEO-102 on immunologic correlates are still ongoing. The authors concluded that treatment with NEO-102 in patients with refractory mCRC resulted in excellent tolerability, a favorable toxicity profile, and encouraging OS. Combination trials with NEO-102 plus chemotherapy are under way.

  1. Patel SP, et al. Cancer Immunol Immunother. 2013;62:1011-1019.
  2. Kim RD, et al. ASCO 2016 Gastrointestinal Cancers Symposium. Abstract 500.