Background: The optimal management of potentially resectable pancreas cancer is unknown. The high rates of local and distant failures following surgical resection highlights the need for improvement in both local and systemic therapies. The combination of newer systemic therapies with ablative radiotherapy could be better tolerated and associated with improved treatment outcomes. Methods: Patients with newly diagnosed, previously untreated, non-metastatic pancreatic cancer who were candidates for resection were prospectively enrolled in this single arm study. Patients received a neoadjuvant regimen of 2 cycles of gemcitabine (1000mg/m²)/nab-paclitaxel (125mg/m²) and SBRT (25Gy in 5 fractions). After neoadjuvant treatment patients were restaged and considered for resection. The primary study endpoint was acute toxicity as assessed by CTCAE V 4.0. The primary study hypothesis was that this neoadjuvant regimen would result in Grade 3+ non-hematologic acute toxicity of < 50% (as per RTOG 97-04). Results: Twenty-five patients were accrued to this study. 28% had resectable and 72% had borderline resectable disease (per NCCN criteria). 96% of patients received both cycles of systemic therapy and all 25 patients went on to SBRT and completed the planned radiotherapy course. The rate of acute non-hematologic Grade 3+ toxicity with the neoadjuvant regimen was 20% (5/25). The rate of overall Grade 3+ toxicity with neoadjuvant gemcitabine/nab-paclitaxel was 52% and Grade 3+ non-hematologic toxicity was 17%; exact 80% CI of (8%, 32%). No Grade 3+ acute toxicity was seen with neoadjuvant SBRT and 28% experienced Grade 2 toxicity. 17/25 (68%) patients went on to surgical resection and 93% achieved an R0 resection. Actuarial local control is 77% and medial overall survival is 24 months. Conclusions: A neoadjuvant approach of gemcitabine and nab-paclitaxel followed by SBRT in patients with potentially resectable pancreatic cancer was well tolerated. Given robust patient accrual, the initial enrollment was expanded to 40 patients and accrual is ongoing. Prospective evaluation of this treatment regimen in a randomized fashion is warranted. Clinical trial information: NCT02318095