Abstract 1529P
Background
Liposomal irinotecan + 5-FU/LV is approved for treating patients with mPDAC following progression with gemcitabine-based therapy. Liposomal irinotecan + 5-FU/LV + OX (NALIRIFOX) is being investigated 1L in a phase I/II study of patients with locally advanced/mPDAC. Serum CA 19-9 levels are typically elevated in such patients and post-treatment decreases are associated with prolonged survival. We report exploratory survival analyses from the phase I/II study for subgroups defined by post-treatment changes in CA 19-9 levels.
Methods
Following dose exploration, the regimen of liposomal irinotecan 50 mg/m2 (free base), OX 60 mg/m2, 5-FU 2400 mg/m2 and LV 400 mg/m2, on days 1 and 15 of 28-day cycles, was selected for dose expansion and 25 more patients were enrolled. In total, 32 patients received the selected (maximum tolerable) dose. Tumors (RECIST v1.1) and serum CA 19-9 were assessed at screening, every 8 weeks and at end of treatment (EoT); tumor assessments continued after EoT. Progression-free and overall survival (PFS and OS) were compared across subgroups defined by best change within the first 16 weeks (data cut-off 26 Feb 2020).
Results
In total, 30/32 patients had a baseline CA 19-9 measurement (median 315.5 U/mL, range 2–127115) of whom 22 had measurements by week 16 (analysis set) with median best change –49.4% (range –100%, +376%). Survival data (Table) were similar for patients with above-normal (≥ 37 U/mL) baseline CA 19-9 levels (n = 17; median best change –35.9% [range –100%, +278%]). Table: 1529P
| PFS | PP 50/60 N = 32 | All n = 22 | Analysis set, best CA 19-9 change | |||
| ≥ 20% decrease | ≥ 50% decrease | |||||
| Yes n = 14 | No n = 8 | Yes n = 11 | No n = 11 | |||
| Progressed/died,a n (%) | 17 (53.1) | 12 (54.5) | 6 (42.9) | 6 (75.0) | 4 (36.4) | 8 (72.7) |
| Median, mo (95% CI) | 9.2 (7.69, 11.96) | 9.6 (7.59, 32.30) | 32.3 (7.95, 32.30) | 7.6 (1.48, 9.56) | 11.2 (7.95, NE) | 7.6 (1.48, 32.30) |
| HR (95% CI) | - | - | 0.13 (0.04, 0.50) | 0.33 (0.09, 1.12) | ||
| OS | ||||||
| Died, n (%) | 20 (62.5) | 14 (63.6) | 7 (50.0) | 7 (87.5) | 6 (54.6) | 8 (72.7) |
| Median, mo (95% CI) | 12.6 (8.74, 18.69) | 12.7 (8.74, 22.54) | 22.5 (12.39, NE) | 8.2 (2.50, 18.69) | 22.5 (11.60, 22.54) | 9.2 (4.83, NE) |
| HR (95% CI) | - | 0.24 (0.08, 0.75) | 0.55 (0.19, 1.60) |
a Patients who progressed/died after new therapy or >16 wks after last non-PD assessment were censored.
Conclusions
1L NALIRIFOX reduced CA 19-9 levels in patients with locally advanced/mPDAC. Median OS and PFS were numerically higher in patients with a ≥20% decrease within the first 16 weeks. CA 19-9 is a potential biomarker of post-NALIRIFOX outcomes.
Clinical trial identification
NCT02551991.
Editorial acknowledgement
Dr Heather Lang 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: Travel/Accommodation/Expenses: Amgen. T. Bekaii-Saab: Advisory/Consultancy: Amgen; Advisory/Consultancy: Bayer; Advisory/Consultancy: Boehringer Ingelheim; Advisory/Consultancy: Celgene; Advisory/Consultancy: Genentech/Roche; 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. P.M. Boland: Research grant/Funding (institution): Boehringer Ingelheim; Research grant/Funding (institution): Merck; Research grant/Funding (institution): Boston Biomedical; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Cascadian Therapeutics; Research grant/Funding (institution): Advaxis; Advisory/Consultancy, Research grant/Funding (institution): Bayer; Honoraria (self): Sirtex; Advisory/Consultancy: Merrimack. F. Dayyani: Speaker Bureau/Expert testimony, Research grant/Funding (institution): Amgen; Advisory/Consultancy, Speaker Bureau/Expert testimony: Eisai; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Exelixis; Advisory/Consultancy: Foundation Medecine; Advisory/Consultancy: Genentech; Research grant/Funding (institution): AZD; Research grant/Funding (institution): BMS; Research grant/Funding (institution): Taiho; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ipsen; Spouse/Financial dependant, Spouse employee: Roche Diagnostics; Advisory/Consultancy: QED; Advisory/Consultancy, Speaker Bureau/Expert testimony: Signatera; Speaker Bureau/Expert testimony: Deciphera; Speaker Bureau/Expert testimony: Sirtex. T. Macarulla: Honoraria (self), Advisory/Consultancy: Genzyme; Honoraria (self), Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Sanofi; Honoraria (self), Research grant/Funding (institution): Roche; Honoraria (self): Tesaro; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Shire; Honoraria (self), Research grant/Funding (institution): Lilly; Honoraria (self): Ipsen; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Celgene; Advisory/Consultancy: QDE; Advisory/Consultancy, Travel/Accommodation/Expenses: 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), Travel/Accommodation/Expenses: Bayer; Research grant/Funding (institution): Genentech; Research grant/Funding (institution): Halozyme; Research grant/Funding (institution): Immonomedics; Research grant/Funding (institution): Merrimack; Research grant/Funding (institution): Millennium; Research grant/Funding (institution): Novartis; Research grant/Funding (institution): Novocure; Research grant/Funding (institution): OncoMed; Research grant/Funding (institution): Pfizer; Research grant/Funding (institution): Pharmacylics; Research grant/Funding (institution): Beigen; Travel/Accommodation/Expenses: Merck. 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), award # NCI/NIH P50 CA210964: National Cancer Institute (NCI) of the National Institutes of Health (NIH); Advisory/Consultancy: Bayer; Advisory/Consultancy: Celgene; Advisory/Consultancy: Eisai; Advisory/Consultancy: Exelixis; Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merrimack; Advisory/Consultancy: Vicus. B. Belanger, F. Maxwell, Y. Moore, T. Wang, B. Zhang: Full/Part-time employment: Ipsen. Z.A. Wainberg: Advisory/Consultancy: Ipsen; Advisory/Consultancy: Merck; Advisory/Consultancy: Lilly; Advisory/Consultancy: QED; Advisory/Consultancy: Daiichi; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bayer.