OA03.03 Initial Efficacy and Safety Results of Irinotecan Liposome Injection (nal-IRI) in Patients with Small Cell Lung Cancer

Abstract

Background: SCLC accounts for ~15% of lung cancers, with 5-year survival <10%. 50-90% of patients with extensive disease respond to initial treatment; many rapidly relapse due to acquired resistance to front-line platinum-based chemotherapy. Limited treatment options are available for second-line patients. nal-IRI is a liposomal formulation of irinotecan (topoisomerase-1 inhibitor), utilizing intraliposomal stabilization technology to enable high drug load and in-vivo stability. Method(s): RESILIENT (NCT03088813) is a two-part Phase 2/3 study assessing the safety, tolerability, and efficacy of monotherapy nal-IRI in SCLC patients who progressed on/after a front-line platinum regimen: Part 1 includes dose-finding then dose-expansion. Key eligibility criteria included ECOG PS 0-1 and adequate organ function, with prior exposure to immunotherapy allowed. Eligible patients received nal-IRI 70mg/m2 or 85mg/m2 (free-base equivalent) q2w. Primary endpoints were safety and tolerability. Efficacy assessments included objective response rate (ORR), best overall response (BOR), progression-free survival (PFS), and overall survival (OS). Result(s): 30 patients were treated for >=12 weeks in Part 1 (male, 43%; median age, 60.4y; platinum-resistant, 40%) with tumor assessments q6w. During dose-finding, 5 patients received nal-IRI 85mg/m2 (deemed not tolerable: dose-limiting toxicity) and 12 patients received nal-IRI 70mg/m2 (deemed tolerable: selected for dose expansion). At data cut-off** (median follow-up, 4.4mo), 25 patients had received nal-IRI 70mg/m2. Diarrhea was the most common gastrointestinal adverse events (AEs) (Gr3, 20%). Hematologic AEs included neutropenia (Gr3, 8%; Gr4, 8%), anemia (Gr3, 8%), febrile neutropenia (Gr3, 4%), thrombocytopenia (Gr3, 4%; Gr4, 4%). Preliminary efficacy identified 11 patients with partial responses (ORR 44%), BOR (PR+SD) of 72%, and 12-week disease control rate (DCR12wks PR+SD) of 48%. PFS and OS are not yet mature. Conclusion(s): Part 1 demonstrated encouraging anti-tumor activity for nal-IRI 70mg/m2 in patients with SCLC (ORR: 44%, BOR: 72%). nal-IRI 70mg/m2 was generally well tolerated. Future research is warranted to assess nal-IRI in second-line SCLC. [Figure presented] Keywords: Irinotecan Liposome Injection, Monotherapy, small cell lung cancerCopyright © 2019