The phase 3 RESILIENT trial of irinotecan liposomal injection vs topotecan failed to meet its primary end point of overall survival in patients with previously treated small cell lung cancer.
Treatment with an irinotecan liposomal injection (Onivyde) did not improve overall survival (OS) compared with topotecan in patients with small cell lung cancer (SCLC) who progressed on or after platinum-based chemotherapy, missing the primary end point of the phase 3 RESILIENT trial (NCT03088813).1
Primary analysis results from the study were announced in a press release by Ipsen and showed that although the primary end point was missed, there was a doubling of the objective response rate (ORR)in the irinotecan liposomal injection arm compared with the topotecan arm.
The safety and tolerability of irinotecan liposomal injection in RESILIENT was consistent with the known safety profile of the agent. No new safety signals were observed. The findings will be shared with the regulatory agency, according to Ipsen.
“While the results from the analysis of the RESILIENT trial have not demonstrated an overall survival benefit with Onivyde in patients in second-line small cell lung cancer, we will now work with our teams to analyze the data further before decisions regarding next steps are made. These data confirm the complexities associated with treating small cell lung cancer, said Howard Mayer, MD, executive vice president, head of Research and Development, Ipsen, in a press release.
RESILIENT is a randomized, open-label study. Thirty patients were enrolled in the part 1 dose-finding portion of the study. Part 1 aimed to describe the safety/tolerability of irinotecan liposomal injection administered every 2 weeks and determine the part 2 does of the agent. In part 2, approximately 450 patients were enrolled and assessed for OS in the irinotecan liposomal injection arm vs the topotecan arm.2
Secondary end points explored in the study were progression-free survival, ORR, quality-of-life assessment per the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-C30/LC13) dyspnea scale and EORTC QLQ-C30/LC13 cough scale, and the incidence of treatment-emergent adverse events (AEs), serious AEs, and laboratory abnormalities.
Patients were eligible for the study given they were 18 years of age or older with an ECOG performance status of 0 or 1, a life expectancy of > 12 weeks, histopathologically or cytologically confirmed SCLC, evaluable disease per RECISTs v1.1, radiologically confirmed progression on or after platinum therapy, and adequate bone marrow, hepatic, and renal function. All patients were required to have recovered from toxicities related to prior chemotherapy, surgery, radiotherapy, or anti-neoplastic therapy. At screening, each patient’s electrocardiogram must show no clinically significant findings. Patients with certain types of asymptomatic central nervous system involvement were permitted to enroll.
Pregnant or breast-feeding patients were ineligible to enroll in RESILIENT as were patients with any medical condition that may have interfered with the patient’s ability to consent of the success of study treatment, per the investigators’ decision.Those previously treated with topoisomerase I inhibitor treatment, retreatment with platinum-based regimen, antibody-drug conjugates, or molecular targeted agents, more than 1 line of immunotherapy, or any other additional regimen of prior cytotoxic chemotherapy were not eligible.
Other ineligible patients were those who were unable to discontinue the use of strong CYP3A4 or UGT1A1 inhibitors at least 1 week before irinotecan liposome injection dosing or strong CYP3A4 inducers at least 2 weeks prior to receiving the first dose of irinotecan liposome injection, had investigation therapy administered within 4 weeks of the study treatment, or have a known hypersensitivity to any drug used in the study.
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://bit.ly/3BE0i9p
2. Study of irinotecan liposome injection (ONIVYDE®) in patients with small cell lung cancer (RESILIENT). ClinicalTrials.gov. Updated March 25, 2022. Accessed August 3, 2022. https://clinicaltrials.gov/ct2/show/NCT03088813?term=irinotecan+liposomal+injection+resilient&draw=2&rank=1