P-287 Nanoliposomal irinotecan (nal-IRI)-containing regimens versus nab-paclitaxel plus gemcitabine as first-line therapy in patients with metastatic pancreatic adenocarcinoma (mPAC): a randomized, open-label phase 2 study

Abstract

Introduction: Patients with mPAC have a poor prognosis, with median survival of <1 year. Current standard first-line treatment options include: 5-fluorouracil (5- FU)/leucovorin (LV) + irinotecan + oxaliplatin (FOLFIRINOX) and nabpaclitaxel + gemcitabine. nal-IRI (MM-398) is a nanoliposomal formulation of irinotecan. In the randomized phase 3 NAPOLI-1 study, nal-IRI + 5-FU/LV significantly improved overall survival (OS) compared with 5-FU/LV (6.1 vs 4.2 months; P = 0.012), and was generally well tolerated in patients with mPAC previously treated with gemcitabine-based therapy (Wang-Gillam et al, Lancet. 2016). Based on these results, nal-IRI + 5-FU/LV has been incorporated into ESMO Clinical Practice Guidelines as recommended second-line therapy for gemcitabine-refractory mPAC (Ducreux et al., Ann Oncol. 2015). The current study (ClinicalTrials.gov, NCT02551991) was designed to determine the preliminary safety and efficacy of nal-IRI + 5-FU/LV with or without oxaliplatin, compared with nab-paclitaxel + gemcitabine, in previously untreated patients with mPAC. Methods: This open-label, phase 2 comparative study will be conducted in 2 parts: A safety run-in ( part 1), and a randomized, open-label study ( part 2). Key eligibility criteria include: age ≥18 years; pathologically confirmed pancreatic cancer; unresectable locally advanced or metastatic disease ( part 1) or metastatic disease ( part 2); no prior treatment for metastatic disease; Eastern Cooperative Oncology Group performance status 0-1; no known metastases to the central nervous system; and adequate hematologic, hepatic, and renal function. In part 1, small cohorts of patients will be enrolled following a traditional 3 + 3 dose escalation design (n = ∼ 6-18). The primary objectives of part 1 are to evaluate the safety and tolerability of nal-IRI + 5-FU/ LV + oxaliplatin, to characterize dose-limiting toxicities, and to determine the target dose of oxaliplatin in combination with nal-IRI + 5-FU/LV for part 2. The secondary objective of part 1 is to characterize the pharmacokinetics of nal-IRI + 5FU/ LV + oxaliplatin. In part 2, an additional 150 patients will be randomized 1:1:1 to a nal- IRI + 5-FU/LV + oxaliplatin regimen (arm 1), the nal-IRI + 5-FU/LV combination that previously demonstrated efficacy in the NAPOLI-1 trial (arm 2), and a nabpaclitaxel + gemcitabine control arm (arm 3). The primary objective of part 2 is to assess the efficacy of the nal-IRI-containing regimens (arms 1 and 2) compared with nab-paclitaxel + gemcitabine (arm 3) with progression-free survival as the primary end point. Secondary objectives of part 2 include: OS, objective response rate according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, CA19-9 tumor marker response, health-related quality of life according to the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire core module (EORTC-QLQ-C30) and the European Quality of Life Questionnaire (EQ-5D-5L), and safety. This study is currently recruiting patients.