J1347: A Phase 1/2A Therapeutic, Open Label, Multi-Center Clinical Trial of NPC-1C, a Chimeric Monoclonal Antibody, in Adults with Recurrent, Locally Advanced Unresectable or Metastatic Pancreatic and Colorectal Cancer After Standard Therapy.
PRIMARY OBJECTIVE Determine the safety and tolerability of escalating doses of NPC-1C (NEO-102) monoclonal antibody therapy in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer or metastatic colorectal cancer that express NPC-1C target on tumor. SECONDARY OBJECTIVES Assess pharmacokinetics and select immune responses to the antibody at each dose level.Evaluate evidence of clinical benefit as measured by RECIST criteria and explore impact on overall survival (OS). Explore the immunologic correlates associated with administration of NPC-1C (NEO-102) monoclonal antibody therapy in subjects with metastatic, locally advanced unresectable or recurrent pancreatic cancer or metastatic colorectal cancer that express NPC-1C target on tumor.
INCLUSION: Subjects must meet the following to be eligible to participate: Subjects with histologically confirmed recurrent, locally advanced unresectable or metastatic adenocarcinoma of the pancreas who have progressed after front line chemotherapy based regimen, OR Subjects with histologically confirmed metastatic colorectal cancer who have progressed after at least 2 chemotherapy based regimens. IHC: greater than or equal to 20% of tumor on tissue sections must stain with NPC-1C. Measurable disease (by RECIST v.1.1) Age: between 18 and 85 years of age. Performance Score: Karnofsky greater than or equal to 50% (see Appendix 3). Laboratory tests meet minimum safety requirements: Hemoglobin greater than 8.5 g/dL (may be receiving supportive therapy). ANC greater than or equal to 1,500/mm3. Platelets greater than or equal to 50,000/mm3. Total bilirubin less than or equal to 2.0 mg/dL. ALT/AST greater than or equal to 2.5 times ULN (or less than or equal to 5 times ULN in subjects with liver mets). Creatinine less than or equal to ULN. EXCLUSION: Subjects with any of the following will not be enrolled: History of disseminated or uncontrolled brain metastases or central nervous system disease. Brain metastases will be considered controlled if SD on two consecutive brain MRIs, performed at least 2 months apart, and patient is without seizures. Ascites with abdominal distention; mechanical, non-reversible reason for not being able to eat, or have a likelihood of developing malignant bowel obstruction during the course of the induction phase of treatment; subjects with uncomplicated J-tubes will not be excluded. Any major surgery within four weeks of enrollment. Uncontrolled concomitant illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia. Serious medical or psychiatric. Serious medical or psychiatric illness, including a second malignancy, that could, in the Investigatorâ??s opinion, potentially interfere with the completion of treatment according to this protocol. Pregnant or breast-feeding. Any chemotherapeutic treatment or corticosteroids within 2 weeks of study entry or any biologic therapy within 4 weeks of study entry. Use of concomitant medications associated with a high risk of DtP and prolongation of QT/QTc interval (Appendix 4). History of allergic reaction to Erbitux greater than grade 1. Uncontrolled diabetes. Prior history of a documented hemolytic event. Receiving warfarin.
NPC-1C is a chimeric (human-murine) monoclonal IgG1 antibody against an epitope from a protein with similarity to MUC5AC, derived from a Tumor Associated Antigen (TAA) based vaccine, capable of detecting the TAA expressed in colon and pancreatic cancer tissue. This is a Phase 1/2A, multi-institution study to determine the maximum tolerated dose (MTD) of NPC-1C and to demonstrate safety, pharmacokinetics (PK) and immune activity. With the release of the new lot of NPC-1C study drug (NEO-102), an additional 3 subjects will be treated at the 1.5 mg/kg dose, and in the absence of serious toxicities, dose escalation will continue using a 3+3 design at doses of 2 mg/kg, 3 mg/kg and 4 mg/kg to assess safety, PK and immune activity. Three subjects will be treated in each cohort until a MTD is identified. A total of 10 subjects will be treated at the MTD.
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