Background: Pancreatic cancer (PC) presents one of the most aggressive malignancies for which currently available treatments are modestly effective. We report the findings of a randomized phase 2 trial (NCT02767557) to test the efficacy of gemcitabine/nab-paclitaxel (gem/nab) with or without tocilizumab (toc), as first-line treatment in patients with locally advanced or metastatic PC. Methods: Prior to randomization, a safety cohort of 6 participants received gem 1000 mg/m2, nab 125 mg/m2 (days 1, 8, and 15 of each 28-day cycle) and toc 8 mg/kg (day 1 of each cycle). Participants were then randomized 1:1 to receive gem/nab or gem/nab/toc. Patients had modified Glasgow Prognostic Score of 1 or 2 and were stratified by performance status (PS) and stage. The primary endpoint was the overall survival (OS) rate at 6 months (OS6). Secondary end points included median progression-free survival (PFS), median OS, overall response rate (ORR), and safety. Results: A total of 147 patients were treated; 141 were randomized to receive gem/nab/toc (n = 70), or gem/nab (n = 71). As of January 9, 2023, the median follow-up was 8.1 months (IQR 4.2–13.9). OS6 was 68.6 % (95% CI, 56.3-78.1) in gem/nab/toc group and 62.0% (95% CI, 49.6-72.1) in gem/nab group (p = 0.41). No significant differences in the median OS or PFS were observed between the gem/nab/toc group and the gem/nab group (OS, 8.4 versus 8.0 months; HR, 0.75; 95% CI, 0.54-1.05; p = 0.10), and (PFS, 5.6 versus 5.5 months; HR, 0.85; 95% CI, 0.61-1.20; p = 0.36). The 12, 18 and 24-month OS rates were 37.1% (95% CI, 26.0%-48.3%), 27.1% (17.4%-37.8%), 10% (4.4%-18.3%) for gem/nab/toc and 28.2% (18.3%-38.9%), 7.0% (2.6%-14.5%), 2.8% (0.5%-8.8%) for gem/nab, respectively. The ORR was 37.1% (95% CI, 25.9%-49.5%) in gem/nab/toc group and 35.2% (24.2%-47.5%) in gem/nab group. The incidence of grade 3 or higher treatment related adverse events was 88.2% in gem/nab/toc and 63.4% in gem/nab group (p < 0.001). Of those, neutropenia (55.3% versus 16.9%), and thrombocytopenia (40.8% versus 11.3%) were most common. Two and one treatment-related deaths, respectively, in gem/nab/toc and gem/nab group, occurred during the study. Conclusions: In patients with advanced PC, the addition of tocilizumab to gem/nab did not result in improved OS rate at 6 months. Although more patients were alive at 18 months in the gem/nab/toc, long-term survival rates exceeding 24 months were not different between groups. The biomarkers for selection of patients who might benefit from gem/nab combined with tocilizumab are to be identified. Clinical trial information: NCT02767557.