Abstract CT415: A Phase I/IIA multicenter clinical trial of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic and colorectal cancer
Authors: Beg Muhammad Shaalan , Morse Michael , Patel Sandip P. , Mavroukakis Sharon , Beatson Melony , Arlen Philip M. , Azad Nilofer S. 
Published: May 2015

Abstract
Background:NPC-1C, (NEO-101 and NEO102, Precision Biologics, Inc) is a novel chimeric monoclonal antibody being developed as a treatment for pancreatic and colorectal cancers. NPC-1C recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. A Phase I trial of NEO-101 has been completed and reported previously. This Phase IIA study utilizes NEO-102, a glycoengineered form of NEO-101 with improved stability and decreased red cell agglutination.
Methods: This is a Phase Ib/IIa, open label, multicenter dose escalation clinical trial with Neo-102 for patients with refractory pancreatic and colorectal cancer. The primary objective is to determine safety, tolerability of escalating doses of NEO-102. Secondary objectives are to assess pharmacokinetics as well as immune response at each dose level, evaluate clinical benefit as measured by RECIST criteria and overall survival, and to explore the immunologic correlates associated with NEO-102. Analyses of patient peripheral blood mononuclear cells (PBMCs) for antibody-dependent cell-mediated cytotoxicity (ADCC) and immune cytokine profiling utilizing the Milliplex MAP Human Cytokine/Chemokine Panel are planned to assess for immunologic outcome, and for correlation with clinical benefit. Patients with histologically confirmed adenocarcinoma of the pancreas who have progressed after front line chemotherapy; or metastatic colorectal cancer who have progressed after at least 2 chemotherapy regimens; whose tumors express the target NEO-102 antigen as defined as ≥ 20% positive stain by NPC-1C immunohistochemistry (IHC) are eligible. Patients have good performance status (KPS ≥ 50%) and adequate hematologic, hepatic and renal function are eligible. Major exclusion criteria include uncontrolled brain metastases, ascites, or other uncontrolled medical illness. Dose escalation was performed in a standard 3+3 design at doses of 1.5mg/kg, 2 mg/kg, 3 mg/kg and 4 mg/kg.
Results: A total of 12 patients (2 pancreatic and 10 colon cancer) have been enrolled. Preplanned dose escalation to the 4 mg/kg dose has been completed and no dose limiting toxicity was observed. Median age is 58 years, 7 are male, median number of prior treatment regimens are 4+ (range 1+ to 8+) Treatment related AEs include grade 1 and 2 diarrhea, fatigue, mucositis, nausea, pruritus, epigastric pain, nasal congestion, insomnia, mouth ulcers, back pain, congestion, weight loss, chills facial flushing and fever, and grade 3 diarrhea and anemia. No severe adverse events (SAE) have been deemed to be drug related. Overall response rate includes 4 patients with PD and 5 patients have achieved SD and 3 patients are too early to evaluate. Median duration of treatment is 56+ days (Range 29 to131+). Conclusions: We have completed dose escalation with NEO-102, a first in man monoclonal antibody with a unique mechanism of action. Treatment is well tolerated with manageable safety profile. Due to encouraging preliminary clinical activity, as demonstrated by disease stabilization in a heavily pretreated population, a Phase II study of NEO-102 monotherapy in pancreatic and colon cancer is now enrolling patients. In addition, a combination study using NEO102 with cytotoxic chemotherapy in metastatic pancreatic cancer is underway.
Citation Format: Muhammad Shaalan Beg, Michael Morse, Sandip P. Patel, Sharon Mavroukakis, Melony Beatson, Philip M. Arlen, Nilofer S. Azad. A Phase I/IIA multicenter clinical trial of the chimeric monoclonal antibody NEO102 (NPC-1C) in adults with refractory pancreatic and colorectal cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr CT415. doi:10.1158/1538-7445.AM2014-CT415