Ipsen Reports Strong Efficacy of Onivyde (Liposomal Irinotecan) Plus Chemotherapy (5-FU/LV + Oxaliplatin) in First-Line Pancreatic Cancer Treatment with Best Overall Response Rate of 81.4%
Jul 03, 2020 11:09
CST Updated
Jul 02, 19:34
Ipsen
Biopharmaceutical Manufacturer
July 02, 2020 News /Bio ValleyBIOON/ -- French pharmaceutical company Ipsen (ipsen) Recently at the European Society for Medical Oncology (ESMO) GastrointestinalTumorPositive results from a Phase I/II study of pancreatic cancer (NCT02551991) were announced at the World Congress on Gastrointestinal Cancer (WCGI).
This is a multicenter, open-label study conducted in patients with previously untreated, unresectable, locally advanced or metastatic pancreatic ductal adenocarcinoma (PDAC), evaluating the safety, tolerability, and dose-limiting toxicities (DLTs) of NALIRIFOX, a combination regimen of Onivyde (liposomal irinotecan injection), 5-fluorouracil/leucovorin (5-FU/LV), and oxaliplatin (OX), as first-line treatment. The study includes a dose-exploration safety lead-in phase (using a traditional 3+3 design) to determine the maximum tolerated dose and the appropriate dosing regimen for NALIRIFOX during the dose-expansion phase. Secondary objectives are to assess clinical efficacy, as determined by median progression-free survival (PFS), median overall survival (OS), best overall response rate (BOR), disease control rate (DCR) at 16 weeks, and duration of response (DOR).
Final analysis as of the data cutoff date of February 26, 2020, including all study participants from the pooled population (n=32: n=7 in the dose exploration phase of Part 1A, Cohort B; n=25 in the dose expansion phase of Part 1B). These patients received Onivyde at the maximum tolerated dose of 50 mg/m² [free], LV 400 mg/m², 5-FU 2400 mg/m², and OX 60 mg/m². Patients were aged ≥18 years, EasternTumorEastern Cooperative Oncology Group (ECOG) performance status score ≤1 and good organ function.
Efficacy results showed: median PFS was 9.2 months (95% CI: 7.69, 11.96), and median OS was 12.6 months (95% CI: 8.74, 18.69). BOR (Best Overall Response) included: 1 case of complete response (CR,Diagnosislocally advanced stage III disease), accounting for 3% (1/32); 10 cases of partial response (PR), accounting for 31.3% (10/32); and 15 cases of stable disease (SD), accounting for 46.9% (15/32). The best overall response rate (BOR: CR+PR+SD) was 81.4%. At week 16, 71.9% (23/32) of the study patients achieved disease control.
Safety results showed: No ≥ Grade 3 fatigue or peripheral neuropathy was reported.Among the 32 study patients, 22 reported treatment-emergent adverse events (TEAEs) of grade ≥3, including: neutropenia (31.3%), febrile neutropenia (12.5%), hypokalemia (12.5%),Anemia(12.5%), diarrhea (9.4%), nausea (9.4%), and decreased neutrophil count (9.4%); vomiting occurred in 6.3% of patients.Eight patients reported treatment-emergent adverse events (TEAEs) leading to discontinuation of oxaliplatin alone or all four study drugs (n=8/32), and 26 study patients required dose adjustments due to adverse events.
Onivyde is a liposomal irinotecan injection administered intravenously, approved in the United StatesFDAApproved, in combination with 5-fluorouracil and leucovorin (5-FU/LV), for the treatment of patients with metastatic adenocarcinoma of the pancreas whose disease has progressed following prior gemcitabine-based chemotherapy.
Based on the efficacy results from this Phase I/II study, Ipsen has initiated patient enrollment in the Phase III NAPOLI-3 study (NCT04083235), comparing the efficacy and safety of the NALIRIFOX regimen versus gemcitabine plus nab-paclitaxel as first-line treatment. In May 2016, the U.S. FDA granted Fast Track Designation (FTD) to the NALIRIFOX regimen for the first-line treatment of pancreatic cancer, a designation that allows pharmaceutical companies toFDAConduct early and frequent interactions; if relevant criteria are met, accelerated approval and priority review are permitted, as is rolling submission of New Drug Applications (NDAs).
“Pancreatic cancer is aggressive, and unfortunately, current treatments—including immunotherapies that are transforming outcomes for patients with other solid tumors—have not achieved similar success in pancreatic cancer,” said Dr. Zev Wainberg, MD, Associate Professor of Medicine at the University of California, Los Angeles (UCLA) and Principal Investigator of the Phase I/II study. “We are continuing to explore opportunities to improve outcomes for more patients and extend survival. The median progression-free survival and overall survival data from the Phase I/II trial are highly promising, and we look forward to comparing this regimen with gemcitabine plus nab-paclitaxel in the ongoing Phase III trial in the first-line setting.” (Bioon.com)