Background: The therapeutic options for 2^nd line therapy PDAC remain unsatisfying with 5-FU/LV plus oxaliplatin or nal-irinotecan resulting in a mOS of 5-6 mo. PDAC has been largely refractory to immune-oncology approaches and CD8+ T cells are rare in most PDAC. AM0010 stimulates survival, expansion and cytotoxicity of intratumoral CD8+ T cells. Immune activation, durable stable disease and a 1yr survival of 22.5% was seen in salvage PDAC patients (pts) receiving AM0010 alone. AM0010 has synergistic anti-tumor activity with 5-FU/LV or oxaliplatin in preclinical models. Here we report on the safety, efficacy and overall survival of AM0010 + FOLFOX as 2^nd and later line treatment in PDAC pts. Methods: PDAC pts progressing on a median of 2 prior therapies (range 1-5) were treated with AM0010 (5ug/kg SQ, qd) + FOLFOX (n = 21). The safety population (n = 25) included also 4 pts with prior oxaliplatin / 5-FU. Tumor responses were assessed with irRC. The survival population included all patients without prior platinum containing regimen. Biomarkers included the sequence analysis of blood derived T cells for T cell clonality. Results: AM0010 + FOLFOX, was generally well tolerated. G3/4 TrAEs included thrombocytopenia (56%), anemia (44%), neutropenia (36%) and fatigue (12%). Most cytopenias had a short duration and reaching retreatment criteria within 2-5 days after dose interruption. Dosing AM0010 for 5 days followed by a 2 days dose holiday has avoided G3/4 cytopenias. Grade1/2 but no higher grade neuropathy was observed in 16% of patients. Of 19 evaluable pts, 2 had an irCR, 1 had irPR with 100% reduction in tumor burden, ORR is 15.8%, DCR is 78.9%. With median follow-up of 23.4 months (range 18.9 - 28.9), mPFS was 2.6 mo, mOS was 10.2 mo and 1-year and 2-year survival was 43% and 28.8%, respectively. The expansion of previously non-detected T cell clones correlated with OS > 8 months. Conclusions: AM0010 in combination with FOLFOX is well tolerated in patients with metastatic PDAC, and has a reduced incidence of FOLFOX related neuropathy. Immune activation and overall survival are encouraging in this advanced PDAC population. This regimen is currently being studied in a phase 3 trial. Clinical trial information: NCT02009449