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A phase 1 dose-escalation study of NEO-102 in patients with refractory colon and pancreatic cancer.
- Source :
-
Cancer Chemotherapy & Pharmacology . Sep2016, Vol. 78 Issue 3, p577-584. 8p. - Publication Year :
- 2016
-
Abstract
- <bold>Purpose: </bold>NEO-102 is a novel chimeric IgG1 monoclonal antibody which recognizes a variant form of MUC5AC expressed specifically by human pancreatic and colorectal tumors. Preclinical models have demonstrated encouraging signs of anti-tumor activity through antibody-dependent cell-mediated cytotoxicity.<bold>Methods: </bold>This is a phase 1, dose-escalation trial of NEO-102 (Ensituximab) for patients with refractory pancreatic and colorectal cancer. The primary objective was to determine safety and tolerability of escalating doses of NEO-102. Secondary objectives were to assess pharmacokinetics, anti-tumor activity and biologic correlates. Patients whose tumors express NPC-1 antigen were eligible. Dose-escalation was performed in a 3 + 3 design at doses of 1.5, 2, 3 and 4 mg/kg.<bold>Results: </bold>A total of 19 patients (4 pancreatic and 15 colon cancer) were enrolled at participating institutions in the treatment phase. Most common treatment-related adverse events included anemia, fatigue, fevers, chills and flushing. There was no detectable hemolysis. Of twelve patients evaluable for disease response, the response rate at week 8 included 5 patients with stable disease and 8 patients with progressive disease (PD). Treatment-related grade 3/4 hyperbilirubinemia and anemia were observed at 4 mg/m2. Reversible hypoxia at 3 mg/kg was a dose-limiting toxicity. The maximum tolerated dose was established at 3 mg/kg. Of 74 patients who underwent tissue screening, positive NPC-1 expression was 47 % in colon and 59 % in pancreatic cancer.<bold>Conclusions: </bold>Treatment with the NEO-102, in this first-in-human study, is well tolerated with a manageable safety profile. A maximum tolerated dose of 3 mg/kg has been established. Toxicity profile is typical for this therapeutic class and allows for combination with conventional cytotoxic therapies. [ABSTRACT FROM AUTHOR]
- Subjects :
- *RECTAL cancer treatment
*PANCREATIC cancer treatment
*ANTIBODY-dependent cell cytotoxicity
*MONOCLONAL antibodies
*IMMUNOGLOBULIN G
*PHARMACOKINETICS
*DRUG dosage
*DRUG tolerance
*ANTINEOPLASTIC agents
*CARRIER proteins
*CLINICAL trials
*COLON tumors
*COMPARATIVE studies
*DOSE-effect relationship in pharmacology
*DRUG toxicity
*RESEARCH methodology
*MEDICAL cooperation
*PANCREATIC tumors
*RESEARCH
*RESEARCH funding
*EVALUATION research
*TREATMENT effectiveness
*MEMBRANE glycoproteins
Subjects
Details
- Language :
- English
- ISSN :
- 03445704
- Volume :
- 78
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Cancer Chemotherapy & Pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 117881456
- Full Text :
- https://doi.org/10.1007/s00280-016-3108-5