Gemcitabine, Nab-paclitaxel, Durvalumab, and Oleclumab Before Surgery for the Treatment of in Resectable/Borderline Resectable Primary Pancreatic Cancer

PRIMARY OBJECTIVE:

I. Estimation of major pathological response (MPR) rate (=\< 5% viable tumor cells).

II. Assess the safety of combining immunotherapy (durvalumab and oleclumab) with gemcitabine/nab-paclitaxel as neoadjuvant therapy.

EXPLORATORY OBJECTIVES:

I. Explore the changes in various immune parameters, including PD-L1 and PD-1 expression in the tumor, during treatment and correlate with efficacy outcomes with the goal of biomarker discovery.

II. Radiographic response rate and CA19-9 response to neoadjuvant therapy. III. Estimate the relapse-free survival (RFS) and overall survival (OS) in enrolled subjects who undergo surgical resection.

IV. Estimate the frequency of intraoperative and postoperative complications in these patients treated with neoadjuvant therapy.

V. Impact of adjuvant durvalumab/oleclumab +/- gemcitabine/nab-paclitaxel on circulating tumor-derived deoxyribonucleic acid (ctDNA) kinetics.

OUTLINE:

Patients receive durvalumab intravenously (IV) over 1 hour on day 1, oleclumab IV over 1 hour, nab-paclitaxel IV, and gemcitabine IV over 1 hour over 30-40 minutes on days 1 and 15. Treatment repeats every 28 days for 2-6 cycles. Within 4-8 weeks after completion of last cycle of treatment, patients undergo surgical resection. After surgical resection, patient may receive adjuvant therapy with durvalumab and oleclumab, durvalumab, oleclumab, gemcitabine, and nab-paclitaxel, other chemotherapy, or observation only at the discretion of the treating physician.

After completion of study treatment, patients are followed up 28 days and then every 3 months for up to 2 years.