Abstract
3070 Background: NPC-1C is a chimeric mab developed to treat P and CR cancers. This mab was selected from a panel of hybridomas derived from biologically screened, pooled human allogeneic colon cancer tissues. The NPC-1C target appears to be a variant of MUC5AC expressed specifically by human P and CR tumors with minimal cross-reactivity to normal GI mucosa. Methods: A phase IIa study with NPC-1C is enrolling patients (pts) with advanced P and CR cancer refractory to standard therapy. Primary objectives are to measure efficacy by analysis of CT scans pre- and post-therapy, clinical lab tests, and physical examinations. Secondary objectives are to determine safety, pharmacokinetics (PK), and select immune responses to the mab. Analyses of pts 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 correlation with clinical benefit. Results: Pts received 1.5 mg/kg IV of NPC-1C every two weeks. 10 subjects (8 colorectal, 2 pancreatic) have enrolled on study (2/10 non-evaluable). Treatment was well tolerated with grade 1 and 2 constitutional symptoms noted. Coombs positivity was reported in 4/8 pts shortly after the infusions, but only grade 1 hemolysis was reported (in 2/8 patients). There was 1 episode of each of the following grade 3 AE’s: weakness, increased bilirubin, and abdominal pain, possibly related to NPC-1C. 5 of 19 pts treated in this and the phase Ia study demonstrated stable disease (SD) on scans after completing the first course of treatment (4 doses). Conclusions: Preliminary results with NPC-1C show signs of clinical activity based on SD in heavily pretreated pts with P and CR cancer. Safety has been established at the 1.5 mg/kg dose. A new lot of NPC-1C, produced with improved sterility and purification procedures and demonstrating no red cell agglutination, has been manufactured under GMP conditions. We plan to introduce this new lot at the current 1.5 mg/kg dose level. If there are no dose limiting toxicities, we plan to dose escalate to a higher MTD at which we will re-evaluate clinical efficacy. Clinical trial information: NCT01040000.
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