RESILIENT part 1: a phase 2 dose‐exploration and dose‐expansion study of second‐line liposomal irinotecan in adults with small cell lung cancer.

Background: RESILIENT (NCT03088813) is a phase 2/3 study assessing the safety, tolerability, and efficacy of liposomal irinotecan monotherapy in patients with small cell lung cancer and disease progression on/after first‐line platinum‐based therapy. Here, we present results from RESILIENT part 1. Methods: This open‐label, single‐arm, safety run‐in evaluation with dose‐exploration and dose‐expansion phases included patients ≥18 years old with Eastern Cooperative Oncology Group performance status of 0/1; those with asymptomatic central nervous system metastases were eligible. The primary objectives were to evaluate safety and tolerability and recommend a dose for further development. Efficacy end points were objective response rate (ORR), progression‐free survival (PFS), and overall survival (OS). Results: During dose exploration, 5 patients received intravenous liposomal irinotecan at 85 mg/m2 (deemed not tolerable; dose‐limiting toxicity) and 12 patients received 70 mg/m2 (deemed tolerable). During dose expansion, 13 additional patients received intravenous liposomal irinotecan at 70 mg/m2. Of these 25 patients (median age [range], 59.0 [48.0‐73.0] years, 92.0% with metastatic disease), 10 experienced grade ≥3 treatment‐related treatment‐emergent adverse events (TEAEs), most commonly diarrhea (20.0%) and neutropenia (16.0%), and 3 had serious treatment‐related TEAEs, of whom 2 died. ORR was 44.0% (95% confidence interval [CI]: 24.40‐65.07; 1 complete response, 10 partial responses) and median (95% CI) PFS and OS were 3.98 (1.45‐4.24) months and 8.08 (5.16‐9.82) months, respectively. Conclusion: Overall, no new safety signals were identified with liposomal irinotecan, and antitumor activity was promising. RESILIENT part 2, a randomized, controlled, phase 3 study of liposomal irinotecan versus topotecan, is ongoing. Lay Summary: Small cell lung cancer (SCLC) is an aggressive disease with few treatment options after platinum‐based therapy.Administering 1 option, irinotecan, as a "liposomal" formulation, may extend drug exposure and improve outcomes.The RESILIENT part 1 trial assessed the safety and efficacy of liposomal irinotecan in 25 adults with SCLC after disease progression despite platinum‐based therapy.No new safety concerns were reported.The most common moderate‐to‐severe side effects were diarrhea (20% of patients) and neutropenia (16%).Tumors responded to treatment in 44% of patients.Average survival was 8.08 months, and time to disease progression was 3.98 months.Liposomal irinotecan trials are ongoing. The phase 1/2 RESILIENT part 1 trial identified no new safety signals with liposomal irinotecan in adult patients with small cell lung cancer whose disease had progressed despite treatment with platinum‐based therapy. The response of tumors to treatment was promising (observed in 44% of patients) and is under further investigation in RESILIENT part 2, a randomized, controlled, phase 3 study of liposomal irinotecan versus topotecan. [ABSTRACT FROM AUTHOR]