On September 8, 2019 Ipsen (Euronext: IPN; ADR: IPSEY) and Servier reported initial safety and efficacy data from Part 1 of the Phase II/III RESILIENT study of investigational liposomal irinotecan (ONIVYDE) in patients with small cell lung cancer (SCLC) who progressed following a first-line platinum-based regimen (Press release, Ipsen, SEP 8, 2019, View Source [SID1234539356]). The results, which included preliminary safety and efficacy data, were presented as an oral presentation at the IASLC 2019 World Conference on Lung Cancer hosted by the International Association for the Study of Lung Cancer in Barcelona, 7-10 September 2019.

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The RESILIENT (NCT03088813) trial is a randomized, open-label two-part Phase II/III study assessing the safety, tolerability and efficacy of investigational liposomal irinotecan as a monotherapy for SCLC patients who have progressed on or after a first-line platinum-based regimen. The trial is being conducted in two parts. Part 1 includes dose-finding and dose-escalation analyses to determine the appropriate dose of study drug where the primary endpoints are safety and tolerability. Part 2 has just been initiated with the first patients randomized and will focus on efficacy assessments versus the current standard of care, topotecan, including progression-free survival (PFS) and overall survival (OS).

"Immunotherapies and combination therapies have proven beneficial in the first-line setting, but despite these advances, many small cell lung cancer patients rapidly relapse due to the aggressive nature of the disease," said Luis G. Paz-Ares, M.D., Ph.D., lead investigator and chief physician, Hospital Universitario 12 de Octubre, Madrid. "While the current standard of care in the second-line setting can extend survival, treatment toxicity has prevented some patients from receiving the full recommended dose. There is a clear need for more treatment options that may give more patients the chance to remain on therapy. It is positive that the RESILIENT trial will continue to investigate this."

ONIVYDE (liposomal irinotecan) is a topoisomerase inhibitor featuring a liposomal formulation of irinotecan that is designed to prolong its circulation before conversion to its active form. This unique mechanism of delivery was evaluated in the NAPOLI-1 Phase III study, which led to the U.S. Food and Drug Administration (FDA) and European Medicines Agency (EMA) approval of ONIVYDE in combination with fluorouracil (5-FU) and leucovorin (LV) for the treatment of metastatic pancreatic cancer following gemcitabine-based therapy. ONIVYDE is not indicated as a single agent for the treatment of patients with metastatic adenocarcinoma of the pancreas.

"ONIVYDE has been proven to help many metastatic pancreatic cancer patients whose disease has progressed following gemcitabine-based therapy to live longer," said Yan Moore, M.D., Ipsen’s Senior Vice President, Head of Oncology Therapeutic Area. "By applying this research to other hard-to-treat-cancers, like small cell lung cancer, we aim to evaluate the potential benefit investigational ONIVYDE may bring to patients who otherwise would have limited treatment options."

"The data presented today shows that further research is warranted, and we look forward to working with Ipsen and our investigators to understand the full potential of bringing new treatment options to small cell lung cancer patients," said Patrick Therasse, M.D., Ph.D., Head of Servier Research and Development Oncology.

Part 1 of the study enrolled 30 patients (median age = 60 (48-73) years) who were treated every two weeks for >12 weeks, with tumor assessments taking place every six weeks. During the dose-finding phase, five patients received liposomal irinotecan 85mg/m2. This dose was deemed not tolerable due to dose limiting toxicity. An additional 12 patients received liposomal irinotecan 70mg/m2, which was deemed tolerable. Thirteen more patients were enrolled in the dose expansion phase of the study at this dose. As of the May 8, 2019 data cut off, a total of 25 patients had received liposomal irinotecan 70mg/m2.

Safety Results:

Liposomal irinotecan 70mg/m2 was generally well-tolerated with Grade 3 or higher treatment emergent adverse events (TEAEs) reported by 10 out of 25 patients.
Diarrhea was the most common Grade 3 gastrointestinal TEAE (n=5).
Hematologic Grade 3 or higher TEAEs included neutropenia (n=4) anemia (n=2) and thrombocytopenia (n=2).
One reported instance of Grade 3 or higher fatigue.

Efficacy Results:

Best overall response (partial response plus stable disease) was 72% with an objective response rate of 44%.
44% (11/25) of patients achieved a partial response with 68% of patients (17/25) experiencing tumor shrinkage.
48% of patients maintained disease control at 12-weeks (DCR12wks PR+SD).
Data for OS and PFS are still maturing.