LBA61 - HR070803 plus 5-FU/LV versus placebo plus 5-FU/LV in second-line therapy for gemcitabine-refractory locally advanced or metastatic pancreatic cancer: A multicentered, randomized, double-blind, parallel-controlled phase III trial (HR-IRI-APC)

Background

Irinotecan liposome plus 5-FU/LV is one of the standard therapy for metastatic pancreatic cancer(mPC) with failed to gemcitabine-based therapy. HR070803 is a liposome formulation of irinotecan and this study aimed to investigate the efficacy and safety of HR070803 plus 5-FU/LV versus placebo plus 5-FU/LV as the second-line treatment in patients with locally advanced pancreatic cancer(LAPC) or mPC who failed to gemcitabine-based therapy.

Methods

Patients (pts) were randomly assigned (1:1) to receive HR070803 56.5 mg/m² (based on irinotecan free base) plus 5-FU/LV 2000/200mg/m² (arm A) or placebo plus 5-FU/LV 2000/200mg/m² (arm B). Randomization was stratified by serum albumin level, treatment history of fluorouracil, treatment history of gemcitabine. The primary endpoint was overall survival (OS). Secondary endpoints were progression-free survival(PFS), objective response rate(ORR) and safety profile, etc. The analysis was based on 228 deaths, with a cutoff date of Nov 18, 2021.

Results

From January 2018 to May 2021, 298 pts were randomly assigned. At a median follow-up of 12.81 months, the primary endpoint with mOS of 7.39 months (95%CI: 6.05-8.41) and 4.99 months (95%CI: 4.27-6.01) in arm A and arm B has met (HR =0.63, 96.4% CI: 0.48-0.84; P=0.0019). Secondary endpoint mPFS was 4.21 months (95%CI: 2.92-5.59) vs. 1.48 months (95%CI: 1.41-1.58) (HR =0.36, 95% CI: 0.27-0.48; P<0.0001), and ORR was 12.75% (95%CI: 7.86-19.20) vs. 0.67% (95%CI: 0.02-3.68) (P<0.0001). In the safety population of 296 pts, the most common grade ≥3 AEs in arm A were γ-GGT elevations (19.05%) and neutropenia (12.93%). The incidence of all grade and grade≥3 diarrhea was 45.58% and 4.08%, neutropenia was 33.33% and 12.93%, cholinergic syndrome was 1.36% and 0% in arm A.

Conclusions

HR070803 plus 5-FU/LV demonstrated a highly statistically significant and clinically meaningful improvement in OS in treatment of locally advanced or metastatic PC with prior gemcitabine-based therapy. Along with a manageable safety profile, these data suggest HR070803 plus 5-FU/LV is a new treatment selection for the population.

Clinical trial identification

NCT05074589.

Editorial acknowledgement

Legal entity responsible for the study

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.