A phase-I study of 90Y-hPAM4 (humanized anti-MUC1 monoclonal antibody) in patients with unresectable and metastatic pancreatic cancer

1664 Objectives: To investigate the safety, tolerability, pharmacokinetics (PK), and dosimetry of single-dose 90Y-DOTA-hPAM4 in patients with pancreatic cancer. Methods: Stage III (after failing one line of chemotherapy)and stage IV (with or without Pancreatic cancer patients were eligible for the study. The patients initially received 111In-hPAM followed by serial imaging and serum samples obtained over 7 days, for PK and to ensure an acceptable biodistribution and organ radiation dose for intended therapy. Patients then received a single infusion of 90Y-hPAM4 with the 90Y dose escalated in cohorts of 3-6 patients (5-mCi/m2 increments) until 2 evaluable patients/cohort encounter dose-limiting toxicity (DLT). DLT was defined as grade 4 toxicity lasting more than 7 days. NCI’s CTC v3 toxicity grades were used to classify adverse events. CT-based measurements were used to evaluate tumor response 4, 8, and 12 weeks after therapy. Results: Eleven patients (5 women, 6 men, ages 34-77) were studied. Nine patients with Stage IV and 2 patients with Stage III disease received 90Y-hPAM4 at an administered activity levels of 15 mCi/m2 (n=3), 20 mCi/m2 (n=5), and 25 mCi/m2 (n=3). 2 patients were chemotherapy naive (0.6 median yrs from diagnosis), 9 patients had previously received systemic therapy predominantly with gemcitabine regimens (1.7 median months from prior treatment). Pre-therapy 111In-hPAM imaging showed acceptable biodistribution and organ radiation dosimetry in all patients. The only significant drug-related toxicity was to the bone marrow. DLT was observed in 1/5 of patients treated at 20 mCi/m2, and 3/3 at 25 mCi/m2 levels. One patient at 15 mCi/m2, and 2 patients at 20 mCi/m2 level achieved objective CT responses in target lesions at 4 wks after treatment. 2 additional patients at different dose schedules had stable target lesions by CT for the same time period. All patients showed disease progression at or after week 8. Conclusions: The MTD for a single administration of 90Y-hPAM is 20 mCi/m2 with bone marrow being the dose-limiting organ. Based on this Phase-I experience, combined/sequential treatment with chemotherapy and fractionated radioimmunotherapy are being considered for future trials. Research Support (if any): Immunomedics