Single-Agent Liposomal Irinotecan Fails to Meet OS End Point in Second-Line Treatment of SCLC

Howard Mayer, MD

Liposomal irinotecan (Onivyde) did not provide an overall survival (OS) benefit compared with topotecan as a second-line treatment for patients with small cell lung cancer (SCLC) who progressed on or after first-line platinum-based chemotherapy, failing to meet the primary end point of part 2 of the phase 3 RESILIENT trial (NCT03088813).¹

Although liposomal irinotecan failed to provide an OS benefit vs topotecan, patients in the experimental arm did achieve a doubling of the objective response rate (ORR) compared with patients in the topotecan arm. Detailed results from RESILIENT will be presented at an upcoming medical conference.

“While the results from the analysis of the RESILIENT trial have not demonstrated an OS benefit with [liposomal irinotecan] in patients in second-line SCLC, we will now work with our teams to analyze the data further before decisions regarding next steps are made,” Howard Mayer, MD, executive vice president and head of Research and Development at Ipsen, stated in a press release. “These data confirm the complexities associated with treating SCLC. We wish to thank the patients, their families, and health care teams for their participation in this clinical trial."

In December 2020, the FDA granted fast track status to liposomal irinotecan as a second-line treatment for patients with SCLC, based on prior results from the phase 2/3 RESILIENT trial.²

Part 1 of the RESILENT trial served as an open-label, dose-establishing study that enrolled 30 patients to find the optimal single-agent dose of liposomal irinotecan and evaluate the agent’s safety and tolerability. The randomized part 2 portion of the study evaluated the efficacy of liposomal irinotecan vs topotecan.

The trial enrolled adult patients aged at least 18 years of age with histopathologically or cytologically confirmed SCLC with evaluable disease per RECIST v1.1 criteria who had radiologically confirmed progression on or after first-line platinum-based chemotherapy or chemoradiation including platinum-based chemotherapy for treatment of limited- or extensive-stage SCLC.³ Notably, patients were permitted to have one line of immunotherapy as monotherapy or in combination in the first- or second-line setting. Additional inclusion criteria included an ECOG performance status of 0 or 1, and a life expectancy of more than 12 weeks.

Patients were excluded from the trial if they had large cell neuroendocrine lung carcinoma; received prior topoisomerase I inhibitor treatment, retreatment with a platinum-based regimen, antibody-drug conjugates or molecular targeted agents, more than one line of immunotherapy, or any other additional regimen of prior cytotoxic chemotherapy; or had symptomatic central nervous system metastasis (CNS) and/or developed new or progressive CNS metastasis within 3 months following prophylactic and/or therapeutic cranial radiation.

In part 2 of the trial, approximately 450 patients were enrolled to receive either intravenous (IV) liposomal irinotecan or IV topotecan.

Along with the primary end point of OS in part 2, secondary end points consisted of ORR, progression-free survival, quality of life, and safety.

The press release noted that results from part 2 of the trial showed that the safety of liposomal irinotecan was consistent with previously reported studies.

In October 2015, the FDA approved the combination of liposomal irinotecan with fluorouracil (5-FU) and leucovorin for the treatment of patients with metastatic adenocarcinoma of the pancreas after disease progression following gemcitabine-based therapy.⁴ Additionally, in June 2020, the FDA granted fast track status to liposomal irinotecan for use in combination with 5-FU/leucovorin and oxaliplatin as a treatment for patients with previously untreated, unresectable, locally advanced or metastatic pancreatic ductal adenocarcinoma.⁵

References

1. Ipsen announces results from phase III RESILIENT trial evaluating Onivyde in second-line monotherapy for small cell lung cancer. News release. Ipsen. August 3, 2022. Accessed August 3, 2022. https://yhoo.it/3BE98nn
2. 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. Accessed August 3, 2022. https://bit.ly/2Jgyi2R
3. Study of irinotecan liposome injection (Onivyde) in patients with small cell lung cancer (RESILIENT). ClinicalTrials.gov. Updated March 25, 2022. Accessed August 2, 2022. https://clinicaltrials.gov/ct2/show/NCT03088813 
4. FDA approves new pancreatic cancer drug. Press release. HealthDay. October 22, 2015. Accessed August 3, 2022. https://bit.ly/3BEk8Bp
5. Ipsen receives FDA fast track designation for liposomal irinotecan (Onivyde) as a first-line combination treatment for metastatic pancreatic cancer. News release. Ipsen. June 17, 2020. Accessed August 3, 2022. https://bit.ly/2BkyKbG