Background: Cremophor EL(CrEL), used to enhance drug solubility, may add paclitaxel’s toxicities such as hypersensitivity reactions or peripheral neuropathy. The rationale for developing an alternative paclitaxel formulation concerns CrEL-related side effects, and a novel paclitaxel delivery system might augment its therapeutic efficacy. GENEXOL-PM (GPM) is a novel polymeric micelle formulated paclitaxel free of CrEL. This is to report the efficacy and safety of the weekly combined chemotherapy with GPM and gemcitabine in patients with recurrent and metastatic adenocarcinoma of the pancreas conducted in multicenter, Republic of Korea. Methods: This was a multicenter, phase 2 study of weekly GENEXOL-PM plus gemcitabine in subjects with recurrent and metastatic adenocarcinoma of the pancreas. The patients who had met the inclusion/exclusion criteria were enrolled and received GPM (125 mg/m²) and gemcitabine (1000 mg/m²) intravenously on day 1, 8, and 15 in every 4 weeks, unless definite disease progression was confirmed. Tumor evaluation was conducted at the end of every 2 cycles according to Response Evaluation Criteria in Solid Tumors (RECIST). Pre-planned test and adverse reaction evaluation were managed after each cycle of drug administration and before the next cycle. The primary end point of this study was objective response rate, and the secondary end points were toxicity, progression free survival and overall survival. Results: Between January 2016 and February 2022, total 32 patients were enrolled; median age was 65 years; male (n=16) and female (n=16). 26 patients were assessable for efficacy. Overall response rate was 19.2% (5/26 patients) and clinical benefit rate (partial response + stable disease) was 34.6% (9/26 patients). The median progression-free survival and overall survival were 8 months, 22 months, respectively. The median number of cycles administered was 5.0 (range=1-21). Most common grade 3 or higher hematological toxicities were: neutropenia occurred in 9 patients (29.0%), neutrophil count decrease 5 patients (16.1%) and anemia 5 patients (16.1%). The most common grade 3/4 non-hematological toxicities were generalized muscle weakness 3 patients (11.5%), pneumonitis 3 patients (11.5%) and liver abscess 2 patients (4.3%). Conclusions: Treatment of advanced pancreatic cancer with combination of GENEXOL-PM and gemcitabine was generally well tolerated and showed a favorable toxicity profile. In this study, efficacy results of combination regimen were comparable to that observed historically with albumin-bound paclitaxel and gemcitabine combination. This regimen demonstrated chemotherapeutic effects to warrant further development when used as first-line chemotherapy for advanced pancreatic cancer. Future studies directly comparing GENEXOL-PM and albumin-bound paclitaxel are required. Clinical trial information: NCT02739633.