LAPNet1: Phase 1b study investigating the association of NP137 with mFOLFIRINOX in locally advanced pancreatic ductal adenocarcinoma.

Abstract

e16441 Background: Pancreatic ductal adenocarcinoma is one of the most lethal malignancies with a 5-year survival rate under 5%. Locally advanced pancreatic ductal adenocarcinoma (LAP) represents 30-40% of cases at the diagnosis, with an overall survival around 15 months. Optimizing chemotherapy in LAP is still a huge challenge. A concomitant inhibition of epithelial mesenchymal transition (EMT) process may potentiate chemotherapy efficacy and decrease the development of resistances. Netrin-1 is upregulated in many metastatic cancers including 60% of pancreatic cancer and promotes tumor invasiveness and metastases development through EMT induction. NP137, a first-in-class anti-Netrin-1 monoclonal antibody, has shown in phase I study the ability to inhibit EMT, potentially overcoming resistance (Cassier et al., Nature, 2023). The goal of LAP-NET1 (NCT05546853) is to evaluate the safety and efficacy of the combination of modified FOLFIRINOX with anti-Netrin-1 targeting (NP137). Methods: LAP-NET1 is a phase 1b multicentric trial studying the combination of modified FOLFIRINOX with NP-137 every 2 weeks for 12 cycles in patients naive of systemic treatment with LAP according to National Comprehensive Cancer Network criteria. A safety lead-in phase will initially enroll 3-12 patients to confirm the recommended dose of NP137 (14 or 9 mg/kg) according to a 3+3 de-escalation protocol, followed by an expansion phase of 40 patients. The primary endpoint is the proportion of patients experiencing adverse events (AEs) of any grade and grade 3/4 AEs (CTCAE v 5.0) related to the experimental treatment at 6 months. Secondary endpoints are best overall objective response according to RECIST 1.1, 12-month progression-free survival (PFS-12m), 12-month overall survival (OS-12m), surgical resection rate, quality of life (EORTC QLQ-C30), time to deterioration and ancillary outcomes based on spatial transcriptomic and classic bulk RNA sequencing. Clinical trial information: NCT05546853 .