First safety analysis of an open-label, single arm phase II trial investigating the efficacy, safety and quality of life of neoadjuvant chemotherapy with liposomal irinotecan combined with oxaliplatin and 5-fluoruracil/folinic acid followed by curati

4172 Background: Aim of the prospective single arm HOLIPANC trial (NCT04617457) is to evaluate the efficacy and safety of multimodal treatment in pancreatic oligometastatic disease. Methods: Patients with hepatic oligometastatic pancreatic cancer receive up to 8 cycles of a combination of liposomal irinotecan (nal-IRI, 50mg/m 2 ) with 5-fluouracil (5-FU 2400mg/m 2 )/folinic acid (FA, 400mg/m 2 ) and oxaliplatin (OX, 60mg/m 2 ) (Nal-IRIFOX) as neoadjuvant therapy followed by curative intended surgical resection of the primary tumor and liver metastases. Here, we present the first preplanned safety analysis with patients (pts) that were enrolled between 10/2021 and 04/2024. Results: A total of 56 pts were included in the analysis, of which 43 (77%) pts received at least 4 cycles and 16 (29%) pts 8 cycles of chemotherapy. Dose reductions of nal-IRI were required in 24 (43%) pts. Treatment-emergent adverse events (TEAE) were observed in 52 (93%) pts, 40 (72%) TEAEs were related to the neoadjuvant chemotherapy. Grade 3-4 TEAEs occurred in 30 (54%) pts, most common were gastrointestinal disorders, i.e. diarrhoea (n = 5), vomiting (n = 4) and nausea (n = 4). Hepatobiliary disorders (cholangitis (n = 5), cholestasis (n = 4)) and increased gamma-glutamyltransferase (n = 4) were also frequent but generally not considered in relation to the chemotherapy. Grade 3 anemia and leukopenia were observed in 3 (5%) and 2 (4%) pts respectively. Serious TEAEs occurred in 23 patients (41%). Next to the above mentioned gastrointestinal and hepatobiliary disorders, dehydration (n = 3) and infections (n = 2) were the remaining recurring events. At the time of analysis, resection was performed in 20 pts (36%). Overall postoperative complications occurred in 7 pts (35%), n = 2 (10%) were classified as Dindo-Clavien grade ≥ 3. Clinically relevant pancreatic fistula was shown in 1 patient (5%). While there were no deaths related to chemotherapy or surgery, 2 pts died because of tumor progression during follow-up within 28 days of chemotherapy administration or surgery. Conclusions: This analysis shows for the first time safety data from a prospective clinical trial of multimodal treatment in oligometastatic pancreatic cancer. As we show, the concept of neoadjuvant chemotherapy followed by surgery is safe, the toxicity and overall morbidity is not elevated compared to available data from the NAPOLI-3 trial, even in combination with a following tumor resection after neoadjuvant treatment. Clinical trial information: NCT04617457 .