4616 Background: Talabostat is an oral small molecule inhibitor of fibroblast activation protein (FAP), a stromal enzyme with collagenase and dipeptidyl peptidase activity. Talabostat also upregulates cytokine and chemokine production, resulting in immune stimulation. Talabostat is active in pancreatic tumor xenograft models and enhances the activity of gemcitabine in mice. Therefore, a clinical trial in patients with metastatic pancreatic cancer was initiated. Methods: Open-label, single-arm, Phase 2 study in 60 evaluable patients with Stage IV pancreatic cancer. Study treatment is administered in 4 x 4-week cycles; gemcitabine 1g/m2 weekly for 4 weeks in Cycle 1, then once weekly for 3 of 4 weeks. Talabostat 200mcg tablets are given BID for 6 days following each gemcitabine infusion; dose-escalation to 300mcg BID is allowed post-Cycle 1. Either agent alone or in combination can be continued beyond 4 cycles depending on tolerability. Eligible patients have measureable Stage IV pancreatic adenocarcinoma (per RECIST) are chemotherapy-naive, have a KPS ≥50, no CNS metastases, transaminases < 3 X ULN, and total bilirubin < 1.5 X ULN. Primary endpoint is 6-month survival with secondary endpoints of overall survival, PFS, pain, and quality-of-life. Tumor response or PD is assessed per RECIST. Results: As of the cut-off date, 46 patients (30 men, 16 women, median age 66 [range 43–88 years]) have received study treatment. Most patients (76%) were Stage IV at original diagnosis, and 72% have a KPS of 80 or higher. Ten of 21 evaluable patients treated as of June 30, 2006 meet 6-month survival. Median overall survival is currently estimated at 4.8 months (95% CI: 2.9, NE) in all 46 patients, and median PFS at 3.5 months (95% CI: 2.0, 4.9). Tumor responses have been reported in 3 patients: one CR and 2 PRs. Pain and QOL have not yet been analyzed. AEs are consistent with those of gemcitabine, with the exception of edema in 28.3% of patients. Grade 3 anemia, neutropenia, hyponatremia hyperbilirubinemia, and increased alk phos are reported in 2 patients each. No Grade 4 AEs have been reported in more than one patient. Conclusions: Talabostat/gemcitabine shows activity in metastatic pancreatic cancer and can be safety administered. Enrollment completed in early January 2007, and final results will be presented at the annual meeting. No significant financial relationships to disclose.
A multinational phase 2 study of nanoliposomal irinotecan sucrosofate (PEP02, MM-398) for patients with gemcitabine-refractory metastatic pancreatic cancer
