FDA Grants Fast Track Status to Irinotecan Liposome Injection for Second-Line SCLC

December 1, 2020 — The FDA has granted a fast track designation to irinotecan liposome injection as second-line monotherapy option for patients with small cell lung cancer whose disease progressed following a platinum-based chemotherapy regimen.

The FDA has granted a fast track designation to irinotecan liposome injection (Onivyde; MM-398) as second-line monotherapy option for patients with small cell lung cancer (SCLC) whose disease progressed following a platinum-based chemotherapy regimen.1

“The fast track designation of [irinotecan liposome injection] as a potential treatment for [patients] living with SCLC is an extension of Ipsen’s focus and contribution to the treatment landscape in oncology,” Howard Mayer, MD, executive vice president and head of research and development at Ipsen, stated in a press release. “With this aggressive and often late-stage diagnosed form of lung cancer, we are proud to be one step closer to making another treatment option available to patients.”

In the open-label, 2-part phase 2/3 RESILIENT trial (NCT03088813), investigators are evaluating the safety, tolerability, and efficacy of irinotecan liposome injection monotherapy in patients with SCLC who progressed on or following a frontline platinum-based regimen. 

In part 1, investigators utilized dose-finding and -escalation analyses to identify the appropriate dose of the monotherapy; here, the primary end points were safety and tolerability. In part 2, which was initiated in September 2019, investigators evaluated the efficacy of this approach compared with standard-of-care topotecan. The primary end points for part 2 include progression-free survival and overall survival.

Results from part 1 of the trial presented during the 2019 World Conference on Lung Cancer (WCLC) demonstrated that irinotecan liposome injection led to disease control in almost half of participants.2,3 

The monotherapy elicited a 44% objective response rate (ORR) in 25 patients who received the optimal dose of 70 mg/m2; this included 11 partial responses. Moreover, the best overall response rate with irinotecan liposome injection was 72% (n = 18), and the disease control rate at 12 weeks was 48%. More than half of patients, or 68%, experienced tumor shrinkage to some extent.

A total of 30 patients were included in part 1 of the trial. Participants had a median age of 60 years. In the dose-finding portion, they were administered irinotecan liposome injection at a dose of either 70 mg/m2 or 85 mg/m2 biweekly. However, after the 85 mg/m2 dose resulted in dose-limiting toxicity in 5 patients, the higher dose was determined to be intolerable. Twelve patients received the agent at the 70 mg/m2 dose, and this was determined to be tolerable. Thirteen additional participants received 70 mg/m2, resulting in a total of 25 patients who received the agent at this level.

Among these 25 patients, 40% (n = 10) were male and 88% had an ECOG performance status of 1. The median age of these participants was 59 years and the median time since most recent progressive disease was 3.2 weeks. Two patients had locally advanced disease, while 23 patients had metastatic disease. A total of 12 patients completed the study, 7 continued on study, and 6 patients had died. Two of the deaths reported were due to a treatment-related toxicity.

Forty percent (n = 10) of patients experienced a treatment-emergent adverse effect (TEAE) that was determined to be grade 3 in severity or greater. The most frequently reported gastrointestinal TEAE was diarrhea, which was reported in 5 patients. Grade 3 or higher hematologic TEAEs were also reported, and these included neutropenia (n = 4), anemia (n = 2), and thrombocytopenia (n = 2). One patient experienced fatigue that was grade 3 or greater in severity.

In October 2015, the FDA approved the use of liposomal irinotecan plus 5-fluorouracil and leucovorin for the treatment of patients with metastatic pancreatic cancer following previous gemcitabine-based chemotherapy based on data from the phase 3 NAPOLI-1 trial (NCT01494506).

The regimen plus oxaliplatin (NALFIRINOX) is also being compared with gemcitabine and nab-paclitaxel (Abraxane) in the phase 3 NAPOLI-3 trial (NCT04083235) for use as a frontline treatment in patients with metastatic pancreatic ductal adenocarcinoma. The regimen was granted a fast track designation in June 2020 for this indication.


  1. Ipsen receives FDA fast track designation for investigational irinotecan liposome injection (Onivyde) as a second-line monotherapy treatment for small cell lung cancer (SCLC). News release. Ipsen. November 30, 2020. December 1, 2020. https://bit.ly/2Jgyi2R.
  2. Ipsen and Servier announce initial phase II/III clinical data evaluating investigational liposomal irinotecan (Onivyde) as a second-line treatment for small cell lung cancer (SCLC) at the IASLC 2019 world conference on lung cancer. News release. Ipsen. September 8, 2019. Accessed December 1, 2020. https://bit.ly/2lPeuHL
  3. Paz-Ares L, Spigel D, Chen Y, et al. Initial efficacy and safety results of irinotecan liposome injection (NAL-IRI) in patients with small cell lung cancer. Presented at: IASLC 20th World Conference on Lung Cancer; September 7-10, 2019; Barcelona, Spain. Abstract OA03.03.
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