Neo-adjuvant chemo-immunotherapy in pancreatic cancer: Results of the Australasian Gastrointestinal Trials Group (AGITG) NEO-IMPACT pilot trial.

4189 Background: Despite curative intent surgery and peri-operative chemotherapy for resectable pancreatic ductal adenocarcinoma (PDAC), recurrence rate remains high (>80%). Whilst immunotherapy has not been shown to be effective in the metastatic setting, there may be a scientific rationale for mobilising the immune system before surgery for localised disease to improve outcomes. Methods: NEO-IMPACT is a single arm phase II study testing the feasibility and safety of delivering 12 weeks of neoadjuvant immune checkpoint inhibitor in combination with FOLFIRINOX (3 doses of 1500mg durvalumab q28d + 6 cycles of FOLFIRINOX q14d) for resectable or borderline resectable pancreas cancer. The patients then received 3 months of adjuvant chemotherapy. The primary endpoint was the proportion of patients receiving ≥80% of planned neoadjuvant treatment. A sample size of 20 was calculated to allow 80% power. Secondary endpoints include the proportion of patients missing surgery due to treatment related adverse events (TRAEs); treatment tolerability; RO resection rate; pathological complete response rate; objective response rate. Results: 20 patients with PDAC were enrolled between August 2022 and June 2024, 13 resectable and 7 borderline resectable disease. 17 of 20 patients (85%) completed planned neoadjuvant treatment. Grade 3-4 adverse events (AEs) occurred in 8 patients. The most common was infection (4), febrile neutropenia (1) and nausea (2). 1 patient died from 5FU toxicity due to homozygous loss of DPYD. There were 2 iAEs (colitis and maculopapular rash). 1 patient had TRAE and had to come off trial but proceeded to surgery. 3 patients (1 borderline/2 resectable) became unresectable at assessment for surgery following neoadjuvant therapy. Of the 16 patients who underwent surgery (12 head; 4 neck/tail), 2 had a complete pathological response. 13 had an R0 resection; 3 had an R1 resection. All 16 patients received post operative adjuvant therapy. At a median follow up of 15 months, 5 patients who proceeded to surgery and adjuvant therapy have recurred. Conclusions: Neoadjuvant chemoimmunotherapy is feasible and safe for patients with resectable and borderline resectable pancreas cancer. A 10% CPR rate and 70% R0 resection rate are encouraging, and this approach should be further explored in a larger population. Clinical trial information: ACTRN12622000378729 .