82P - A randomized controlled, open-label, adaptive phase III clinical trial to evaluate safety and efficacy of EndoTAG-1 plus gemcitabine versus gemcitabine alone in patients with measurable locally advanced and/or metastatic adenocarcinoma of the pancreas after FOLFIRINOX

Background

FOLFIRINOX is a global standard first-line (1L) treatment for advanced pancreatic ductal adenocarcinoma (APDAC), but the second-line option after its failure remains yet defined. Current study evaluated the efficacy and safety of EndoTAG-1 (paclitaxel in cationic liposomes) plus gemcitabine as a second-line treatment in APDAC after FOLFIRINOX.

Methods

Patients with histologically confirmed APDAC and failed to 1L FOLFIRINOX were eligible. Participants were stratified by disease stage (metastatic vs. locally advanced) and ECOG performance status (0 vs. 1) and then randomized 1:1 to receive either EndoTAG-1 22 mg/m² twice weekly plus gemcitabine 1000 mg/m² weekly for 3 weeks every 4 weeks (ET+Gem arm) or gemcitabine 1000 mg/m² alone (Gem arm). The primary endpoint was overall survival (OS) of the intent-to-treat population.

Results

A total of 218 patients were enrolled: median age 62.0, 59.6% male, 52.8%/30.3% White/Asian, 86.7% metastatic diseases at enrollment, 44.5%/55.5% ECOG PS 0/1. Of the 108 subjects in the ET+Gem group and 110 subjects in the Gem group, six (5.6%) and eight (7.3%) did not receive assigned treatment, respectively. On intent-to-treat analysis, the median OS for patients in ET+Gem arm was 226 days (95% confidence interval [CI] 183-278) vs. 209 days (158-248) for Gem arm (p=0.665). The median PFS was 113 days (79-168) for the ET+Gem arm vs. 110 days (60-115) for the Gem armp (=0.435), whiles the objective response rate (ORR) in corresponding arm was 11.5% and 6.8%, respectively (p=0.263). Treatment-emergent adverse events (TEAEs) grade 3 and above occurred in 82 patients (82/102, 80.4%) of the ET+Gem arm and 72 patients (72/102, 70.6%) in the Gem arm. Grade 5 / death related to TEAEs occurred for six patients (5.9%) in the ET+Gem arm and 11 patients (10.8%) in the Gem arm.

Conclusions

Add-on EndoTAG-1 did not significantly improve survival over gemcitabine alone in patients with FOLFIRINOX-refractory APDAC. No new safety issues were noted and the safety profile is manageable.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

SynCore Biotechnology Co., Ltd.

Funding

SynCore Biotechnology Co., Ltd.

Disclosure

The author has declared no conflicts of interest.