191P - First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: Results from a phase I/II study

Background

Liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) is approved for adults with metastatic pancreatic ductal adenocarcinoma following progression with gemcitabine-based therapy. We report results from an open-label phase I/II study (NCT02551991) of adults with untreated, unresectable, locally advanced/metastatic PDAC receiving liposomal irinotecan + 5-FU/LV + oxaliplatin (NALIRIFOX).

Methods

Eligible patients were adults with ECOG performance status (PS) ≤ 1 and adequate organ function who received NALIRIFOX (liposomal irinotecan 50 mg/m² (free base), 5-FU 2400 mg/m², LV 400 mg/m², oxaliplatin 60 mg/m²) on days 1 and 15 of each 28-day cycle. The primary endpoint was safety; secondary endpoints included progression-free survival (PFS), overall survival (OS), best overall response, overall response rate (ORR), disease control rate at 16 weeks (DCR₁₆) and duration of response (DoR). RECIST v1.1 was assessed at screening, every 8 weeks and at treatment end.

Results

Overall, 32 patients were included (median [range] age 58.0 [39–76] years; 43.8% men; 87.5% metastatic disease; 56.3% ECOG PS 1). In total, 22 patients experienced grade ≥ 3 treatment-emergent adverse events (TEAEs): neutropenia (31.3%), febrile neutropenia (12.5%), hypokalemia (12.5%), diarrhea (9.4%), nausea (9.4%) and decreased neutrophil count (9.4%). Serious TEAEs were reported in 17 patients: nausea (9.4%) and febrile neutropenia (9.4%). TEAEs led to 3 deaths (none treatment-related), to dose adjustment in 26 and discontinuation in 8 patients. Median (95% CI) PFS and OS were 9.2 (7.69–11.96) months and 12.6 (8.74–18.69) months, respectively. One patient, with locally advanced disease, had complete response, 10 partial response, and 15 stable disease. ORR (95% CI) was 34.4 (18.6–53.2) %, DCR₁₆ was 71.9 (53.3–86.3) % and median (95% CI) DoR was 9.4 (3.52, NE) months.

Conclusions

First-line NALIRIFOX raised no new safety signals in patients with locally advanced/metastatic PDAC; anti-tumour activity was promising. The randomized phase III NAPOLI-3 study (NCT04083235) will compare NALIRIFOX with gemcitabine + nab-paclitaxel.

Clinical trial identification

NCT02551991.

Editorial acknowledgement

Alison Chisholm of Oxford PharmaGenesis, Oxford, UK, provided medical writing and editorial support, which was sponsored by Ipsen, in accordance with Good Publication Practice guidelines.

Legal entity responsible for the study

Ipsen.

Funding

Ipsen.

Disclosure

A. Dean: Non-remunerated activity/ies: Shire; Non-remunerated activity/ies: Specialised Therapeutics; Travel/Accommodation/Expenses: Amgen. T. Bekaii-Saab: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genetech/Rpche; Advisory/Consultancy: Glenmark; Advisory/Consultancy: Lilly; Advisory/Consultancy: Merrimack; Advisory/Consultancy: NCCN; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Research to Practice; Advisory/Consultancy: Sirtex Medical; Advisory/Consultancy: Taiho Pharmaceutical; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Merck; Advisory/Consultancy: Polaris. P.M. Boland: Research grant/Funding (self): Boehringer Ingelheim; Research grant/Funding (self): Merck; Research grant/Funding (self): Boston Biomedical; Research grant/Funding (self): Genentech; Research grant/Funding (self): Cascadian Therapeutics; Research grant/Funding (self): Advaxis; Advisory/Consultancy, Research grant/Funding (self): Bayer; Honoraria (self): Sirtex; Advisory/Consultancy: Merrimack. F. Dayyani: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Research grant/Funding (institution): AstarZeneca; Research grant/Funding (institution): Bristol-Myers Squibb; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Exelixis; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Taiho Pharmaceutical; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy: Foundation Medecine; Advisory/Consultancy: Genetech; Advisory/Consultancy, Speaker Bureau/Expert testimony: Natera; Advisory/Consultancy: QED Therapeutics; Speaker Bureau/Expert testimony: Deciphera Pharmaceuticals; Speaker Bureau/Expert testimony: Sirtex Medical; Spouse/Financial dependant: Roche Diagnostics. T. Macarulla Mercade: Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Speaker Bureau/Expert testimony: Sanofi; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Honoraria (self): Lilly; Honoraria (self): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy: QDE; Advisory/Consultancy: H3B; Advisory/Consultancy: Baxalta; Advisory/Consultancy: Incyte; Advisory/Consultancy: Servier; Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Agios; Research grant/Funding (institution): Aslan; Research grant/Funding (institution): Bayer; Research grant/Funding (institution): Genetech; Research grant/Funding (institution): Halozyme; Research grant/Funding (institution): Immonomedics. K. Mody: Research grant/Funding (institution): Agios; Research grant/Funding (institution): Senwha Biosciences; Research grant/Funding (institution): Taiho; Research grant/Funding (institution): ArQule; Advisory/Consultancy, Research grant/Funding (institution): AstraZeneca; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Incyte; Research grant/Funding (institution): MedImmune; Research grant/Funding (institution): Puma Biotechnology; Research grant/Funding (institution), (NIH) award # NCI/NIH P50 CA210964: National Cancer Institute (NCI) of the National Institutes of Health; Advisory/Consultancy: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Vicus. B. Belanger: Full/Part-time employment: Ipsen. F. Maxwell: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. Y. Moore: Leadership role, Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. A. Thiagalingam: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. T. Wang: Shareholder/Stockholder/Stock options, Full/Part-time employment: Ipsen. B. Zhang: Shareholder/Stockholder/Stock options, Licensing/Royalties, Full/Part-time employment: Ipsen. Z.A. Wainberg: Advisory/Consultancy, Research grant/Funding (institution): Five Prime Therapeutics; Advisory/Consultancy, Research grant/Funding (institution): Ipsen; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Plexxikon; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer; Advisory/Consultancy: Daiichi Sankyo; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Merck; Advisory/Consultancy: QED Therapeutics.