Background: BXCL701 targets DPP8/9 and stimulates migration and cytotoxicity of T and NK cells in addition to targeting fibroblast activator protein (FAP) which forms an immunological barrier to the tumor microenvironment. NKTR-214 is a CD122-biased agonist designed to provide sustained signaling through the heterodimeric IL2 receptor pathway (IL2Rβɣ) to preferentially activate and expand effector CD8+ T and NK cells. NKTR-214 has demonstrated robust anti-tumor activity when combined with anti-PD1 in multiple murine tumor models and recently, with nivolumab in multiple human cancers. We hypothesized that BXCL701 could further potentiate NKTR-214/anti-PD1 anti-tumor activity by removing fibrotic barriers to immune cells. Methods: NKTR-214, BXCL701 and anti-PD1 were dosed in mice bearing established (~100mm³) murine pancreatic tumors (Pan02) as single agents, doublets and the triplet (0.8mg/kg q9d, 20µg qd, and 200 µg qw2 respectively). Tumors were profiled using IHC and multiplex serum cytokine/chemokine analysis. Tumor-free mice were re-challenged with either Pan02 or murine lung tumor (LLC). Results: Of the mice treated with the triplet combination, 100% became tumor-free (9/9) by day 21. These animals remained tumor free for more than 60 days when a subset were re-challenged with new tumor cells. Of these, 5/6 mice rejected tumor regrowth suggesting durable immunity after the triplet therapy. IHC of the tumors from satellite animals sacrificed on day 3 revealed that the triplet significantly reduced FAP expression while increasing the number of immune cell infiltrates in the tumor. Conclusions: The triplet of NKTR-214, BXCL701 and anti-PD1 provided 100% tumor-free mice in established pancreatic tumors with concomitant reduction in FAP expression. The results suggest that removal of fibrotic barriers to immune infiltration is an important mechanism for overcoming immune escape by tumors otherwise resistant to immune therapy. These results provide therapeutic rationale for treatment of pancreatic cancer patients with this triple combination.