What is this summary about?This is a summary of a clinical study called NAPOLI 3. The NAPOLI 3 study included 770 patients with a type of pancreatic cancer called pancreatic ductal adenocarcinoma(PDAC). All of the patients in NAPOLI 3 had metastatic PDAC (mPDAC), meaning that their cancer had spread from their pancreas to other parts of the body. None of the patients had received any previous treatment for metastatic cancer, meaning that they had untreated mPDAC. In NAPOLI 3, the study team wanted to compare a new combination chemotherapy called NALIRIFOX with another chemotherapy combination called GemNabPac in patients with untreated mPDAC. NALIRIFOX includes four chemotherapy drugs: liposomal irinotecan, oxaliplatin, leucovorin and fluorouracil.GemNabPac includes two chemotherapy drugs: nab-paclitaxel and gemcitabine. GemNabPac is a treatment that is already used by doctors and is approved by regulatory agencies in the USA and Europe for patients with untreated mPDAC. This study looked at the survival time of patients, the time for the cancer to worsen after treatment and the side effects of both chemotherapy combinations.What were the results?The study showed that NALIRIFOX increased survival time and the length of time it took for the cancer to worsen compared with GemNabPac. The number and severity of side effects was similar between the two treatments, but the type of side effects differed between the two treatments. Severe side effects that affect the blood were less common with NALIRIFOX than GemNabPac, whereas severe digestive side effects were more common with NALIRIFOX than GemNabPac. There were no new safety concerns for either of the combinations.What do the results mean?NAPOLI 3 is the first study to compare two different combination chemotherapy treatments in patients with untreated mPDAC. The results of NAPOLI 3 mean that NALIRIFOX is a possible treatment option for patients diagnosed with mPDAC. In early 2024, NALIRIFOX was approved by the regulatory agency in the USA (called the US Food and Drug Administration or FDA) and by the regulatory agency in Europe (called the European Medicines Agency or EMA) because of the results of NAPOLI 3. NALIRIFOX is now approved for patients with untreated mPDAC in the USA, Europe (European Union countries and Switzerland), Taiwan, Australia and Egypt, and is the first new treatment approved for people with untreated mPDAC since 2013.[Box: see text].