- Ipsen has initiated the NAPOLI-3 Phase III clinical study (NCT04083235) comparing the safety and efficacy of liposomal irinotecan + 5-fluorouracil/leucovorin (5-FU/LV) + oxaliplatin (OX) (NALIRIFOX) to gemcitabine + nab-paclitaxel in the first-line setting
- Ipsen has been granted Fast Track Designation by the FDA for investigational liposomal irinotecan + 5-FU/LV + OX (NALIRIFOX) for the first-line treatment of patients with metastatic pancreatic cancer
PARIS, FRANCE, 01 July 2020 – Ipsen (Euronext: IPN; ADR: IPSEY), today announced the primary analysis of the Phase I/II study evaluating the investigational use of irinotecan liposome injection (Onivyde®) in combination with 5-fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) together, known as NALIRIFOX in study patients with previously untreated, unresectable, locally advanced and metastatic pancreatic ductal adenocarcinoma (PDAC) during a late-breaking oral presentation at the ESMO World Congress on Gastrointestinal Cancer (WCGI), 1–5 July 2020. The results include safety and efficacy analyses from the multicenter, open-label, study consisting of dose-exploration safety run-in (traditional 3+3 design) to confirm the maximum tolerated dose and appropriate dose regimen for NALIRIFOX in the dose-expansion phase.1
No new safety signals were observed in the 32 patients evaluated from the recommended NALIRIFOX 50/60 mg/m2 dose (primary endpoint). Study patients achieved median progression-free survival of 9.2 months and median overall survival of 12.6 months (secondary endpoints).1
These data, in addition to promising anti-tumor activity highlighted by secondary endpoints, have led to the initiation of patient enrollment for the international Phase III NAPOLI-3 clinical study investigating the safety and efficacy of NALIRIFOX versus gemcitabine + nab-paclitaxel in the first-line setting.2 On 5 June 2020, Ipsen was granted Fast Track designation from the U.S. Food and Drug Administration (FDA) to facilitate the development and potentially expedite the review of NALIRIFOX in this indication. Programs with Fast Track designation may benefit from early and frequent interactions with the FDA over the course of drug development. In addition, the Fast Track designation program allows for the eligibility for accelerated approval and priority review if relevant study criteria are met and enables a company to submit individual sections of a New Drug Application (NDA) for review on a rolling-submission basis.
“Pancreatic cancer is aggressive, and we continue to investigate opportunities to improve outcomes for more patients that can extend survival. Unfortunately, current treatments, including immunotherapies that are transforming outcomes for patients with other solid tumors, have not demonstrated similar success in pancreatic cancer.” said Zev Wainberg, M.D., lead investigator and associate professor of medicine, University of California Los Angeles. “The initial median progression-free and overall survival data from our Phase I/II trial are promising and we look forward to seeing how this investigational first-line treatment compares to gemcitabine + nab-paclitaxel in the Phase III trial now underway.”
“A year following the read out of the preliminary Phase I/II study, we remain encouraged by the data, which demonstrated no new safety signals and continued to show anti-tumor activity,” said Howard Mayer, M.D., Executive Vice President, Head of Research and Development at Ipsen. “Ipsen is committed to patients with pancreatic cancer. We are currently enrolling patients in our NAPOLI-3 Phase III clinical study across the U.S. and in other countries to gain a better understanding of the role of liposomal irinotecan as a potential first-line combination treatment for locally advanced and metastatic pancreatic cancer.”
The Phase I/II, open-label trial (NCT02551991) was designed to assess the safety, tolerability and dose-limiting toxicities (DLTs) of NALIRIFOX for the first-line dosing of study participants with locally advanced and metastatic pancreatic cancer. Secondary objectives were to assess clinical efficacy, defined by median progression-free survival (PFS) and median overall survival (OS), best overall response rate, overall response rate (ORR), disease control rate at 16 weeks (DCR) and duration of response (DoR).1
The final analysis as of the data cut off on 26 February 2020 included all study participants from the pooled population (n=32: Part 1A-cohort B dose exploration phase n=7; Part 1B-dose expansion phase n=25) who received the maximum tolerated dose of liposomal irinotecan 50 mg/m2 [free-base], LV 400 mg/m2, 5-FU 2400 mg/m2, and OX 60 mg/m2). Patients were aged ≥ 18 years with an Eastern Cooperative Oncology Group (ECOG) performance status score ≤ 1 and adequate organ function.1 The preliminary results from this study were presented at the ESMO World Congress on Gastrointestinal Cancer in July 2019.
Phase I/II Safety Results1:
- No reported Grade 3 or higher fatigue or peripheral neuropathy.
- Treatment emergent adverse events (TEAEs) Grade 3 or higher were reported by 22 of 32 study patients and included: 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.
- 8 patients reported TEAEs leading to discontinuation of oxaliplatin alone or all four study drugs (n=8/32), with 26 study patients requiring dose adjustment due to AEs.
Phase I/II Efficacy Results1:
- Study patients saw a median PFS (95% CI) of 9.2 months (7.69, 11.96) and median OS of 12.6 months (8.74, 18.69).
- BOR (Best Overall Response) included: one complete response (CR; study participant diagnosed with locally advanced Stage III disease) in 3% (1/32), 10 partial responses (PR) in 31.3% (10/32) and 15 stable diseases (SD) in 46.9% (15/32) (sum of CR+PR+SD = 81.3%).
- Disease control achieved by 71.9% (23/32) of study patients at 16 weeks.
ABOUT ONIVYDE® (irinotecan liposome injection)
Ipsen has exclusive commercialization rights for the current and potential future indications for Onivyde® in the U.S. Servier is responsible for the commercialization of Onivyde® outside of the U.S. and Taiwan under an exclusive licensing agreement with Ipsen. PharmaEngine has commercial rights to Onivyde® in Taiwan.
INDICATION – UNITED STATES
Onivyde® is approved by the U.S. FDA in combination with fluorouracil (5-FU) and leucovorin (LV) for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy. Limitation of Use: Onivyde® is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.
Please see full U.S. Prescribing Information and Boxed WARNING for ONIVYDE.
About the Phase I/II Study
The Phase I/II, open-label, comparative trial is designed to assess the safety, tolerability and dose-limiting toxicities of investigational irinotecan liposomal injection (Onivyde®) in combination with 5-fluorouracil/leucovorin (5-FU/LV) and oxaliplatin (OX) as a potential first-line treatment for metastatic pancreatic ductal adenocarcinoma cancer patients. The study has enrolled 56 patients at 15 sites across the United States, Spain and Australia. It is being conducted in two parts:
- Part 1a: a safety run-in as initial dose exploration
- Part 1b: dose expansion of the liposomal irinotecan + 5-FU/LV + oxaliplatin regimen
The study’s primary endpoint is safety and tolerability. Secondary assessments of clinical efficacy include overall response rate, disease control rate and best overall response. For more information visit clinicaltrials.gov and use identifier NCT02551991.3
About the NAPOLI-3 Phase III Study
The NAPOLI-3 clinical trial is an open-label, randomized, multicenter, Phase III study of irinotecan liposome injection (Onivyde®) in combination with oxaliplatin (OX) and 5-fluorouracil/leucovorin (5-FU/LV) versus nab-paclitaxel plus gemcitabine in subjects who have not previously received chemotherapy for metastatic adenocarcinoma of the pancreas. The purpose of this study is to look at the efficacy and safety of investigational irinotecan liposome injection in combination with other FDA-approved drugs used for cancer therapy compared to nab-paclitaxel + gemcitabine treatment in improving the overall survival of patients not previously treated for metastatic pancreatic cancer. The study’s primary endpoint is Overall survival (OS), with secondary outcome measures defined as Progression free survival (PFS) and Overall Response Rate (ORR).
Ipsen is currently enrolling patients. To learn more about the study contact firstname.lastname@example.org or visit clinicaltrials.gov and use identifier NCT04083235.2
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- Wainberg, Z.A., et al. First-line liposomal irinotecan + 5 fluorouracil/leucovorin + oxaliplatin in patients with pancreatic ductal adenocarcinoma: long-term follow-up results from a phase 1/2 study. Oral/abstract presented at the ESMO World Congress on Gastrointestinal Cancer (WCGI 2020, abstract #LBA-1). Available at worldgicancer.com/sites/2020v2.worldgicancer.com/files/2020-04/Abstract_Titles_and%20Authors_0.pdf. Accessed: June 2020.
- A Study to Assess the Effectiveness and Safety of Irinotecan Liposome Injection, 5-fluorouracil/Leucovorin Plus Oxaliplatin in Patients Not Previously Treated for Metastatic Pancreatic Cancer, Compared to Nab-paclitaxel+Gemcitabine Treatment (NAPOLI 3). www.clinicaltrials.gov. Accessed: June 2020. Available: https://clinicaltrials.gov/ct2/show/NCT04083235?term=NCT04083235&draw=2&rank=1.
- Study of Nanoliposomal Irinotecan (Nal-IRI)-Containing Regimens Versus Nab-paclitaxel Plus Gemcitabine in Patients With Previously Untreated, Metastatic Pancreatic Adenocarcinoma. www.clinicaltrials.gov. Accessed: June 2020. Available: https://clinicaltrials.gov/ct2/show/NCT02551991?term=NCT02551991&draw=2&rank=1