On October 29th, 2015, Dr. Shi Si gave a wonderful English presentation on “FDA drug approval and new hopes for pancreatic cancer”, about the new drug MM-398, which was just approved by FDA last week, and made his own analysis on the application prospect of the drug in pancreatic cancer. Dr. Shi Si firstly introduced the 5 channels of FDA approval for new drugs. The differences and similarities of 1) Fast Track 2) Priority Review 3) Accelerated Approval 4) Breakthrough Therapies 5) Standard review were explained and analyzed. Due to the poor prognosis of pancreatic cancer itself and the lack of effective therapeutic drugs, all marketed pancreatic tumor-related drugs, starting with gemcitabine, have received Priority Review Designation from the FDA, including sunitinib and everolimus for the treatment of pancreatic neuroendocrine tumors. MM-398, also known as PEP02 and under the trade name Onivyde, is a nanoliposome-encapsulated irinotecan that was developed by PharmaEngine Taiwan and Merrimack, Inc. In the phase I clinical trial, MM-398 showed some antitumor effects in some advanced solid tumors, while its maximum tolerated dose (MTD) was determined to be 120 mg/m2 q3w. In the subsequent phase II clinical study of second-line chemotherapy for advanced gastric cancer, MM-398 did not show superiority in efficacy compared to the control group. Therefore, the company focused on advanced pancreatic cancer, where MM-398 demonstrated efficacy in patients with gemcitabine-resistant metastatic pancreatic cancer in a phase II clinical trial containing 40 patients. 50% of patients achieved disease control (PR or SD for >2 cycles). 31.3% of patients with elevated baseline CA19-9 demonstrated >50% decrease in tumor markers decline, with OS and PFS of 5.2 months and 2.4 months, respectively. Based on the apparent therapeutic effect of MM-398 as a second-line agent in metastatic pancreatic cancer demonstrated in the phase II study. An international multicenter, open-label phase III clinical trial (the NAPOLI-1 study) was conducted. This was a three-arm clinical trial in which 417 patients with metastatic pancreatic cancer who had received prior gemcitabine-based chemotherapy were randomized 1:1:1 to receive the following regimens: MM-398 (120 mg/m2, intravenous, >90 min) every 3 weeks; 5-FU (2000 mg/m2, >24 h), LV (200 mg/m2, >30 min), stopping for 2 weeks at 4 weeks of treatment; MM-398 (80 mg/m2, intravenous, >90 min), 5-FU (2400 mg/m2, >46h), LV (400 mg/m2, >30 min), once every 2 weeks. The primary study endpoint was OS. its full study results have not been published, but were disclosed at both the 2014 ESMO World GI and the 2015 ASCO World GI. Although single-agent MM-398 did not show a clear advantage, the MM-398 combined with 5-FU/LV group showed an improvement in OS and PFS compared to the 5-FU/LV group (OS, 6.1m vs 4.2m; PFS 3.1m vs 1.5m). Based on the results of the NAPOLI-1 study, MM-398 received Priority Review in June 2015, and in October 2015, the MM-398/5-FU/LV regimen was approved for marketing by the FDA as a new chemotherapy regimen for gemcitabine-resistant metastatic pancreatic cancer. Dr. Schiess further analyzed the characteristics and prospects of MM-398, and concluded that MM-398, as a liposomal formulation of irinotecan, could theoretically help the directly acting active drug to enter the tumor and improve the anti-cancer effect of the active drug, while also protecting healthy tissues from the toxic effects of the drug. This is another success story of an old drug with a new formulation, following albumin-bound paclitaxel (nab-paclitaxel) in pancreatic cancer. However, in the phase III clinical trial, the FF regimen (5-FU+LV) was chosen for its control group instead of the current standard second-line regimen, the OFF regimen (OXA+5-FU+LV). the role of the OFF regimen in the second-line treatment of advanced pancreatic cancer was clearly reported in a phase III clinical trial as early as 2001 (CONKO-study group, Eur J Cancer), and its effectiveness is now being further confirmed in clinical practice. Clinicians are faced with a choice among second-line regimens, and considering that there is no evidence that the new regimen is superior to the OFF regimen, and that the new regimen may be more expensive, the use and promotion of MM-398 in the clinic may face some problems. In addition, the status of MM-398 in postoperative adjuvant chemotherapy for pancreatic cancer is not yet known. How to choose the postoperative adjuvant chemotherapy regimen for pancreatic cancer to further improve the effectiveness of surgery is one of the current clinical focus and hotspot. The Pancreatic Surgery Department of the Institute of Pancreatic Oncology/Fudan University Cancer Hospital has pioneered several related studies in the international arena, including GEM+ABX VS GEM (adjuvant, stage II), GEM+MET VS GEM (adjuvant, stage II) GEM+ABX VS OFF (postoperative second-line, stage III, multicenter), etc. Finally, Dr. Schiess briefly reviewed some recent new pancreatic cancer drugs that are still in clinical trials, including RX-3117 and M402, two new orphan drugs for pancreatic cancer approved by FDA in 2014, and TH-302, which was approved by Fast Track in 2015. clinical trials (JCO, 2015), and its Phase III clinical trial (first-line, GEM + TH302 vs. GEM) is still ongoing. This revolutionary drug is likely to change the current treatment of pancreatic cancer for the benefit of pancreatic cancer patients.