Efficacy and safety of ivonescimab combined with liposomal irinotecan in patients with small-cell lung cancer (SCLC) progressing after first-line chemoimmunotherapy: A multicenter, phase 2 study.

Abstract

8007 Background: SCLC patients (pts) progressing after first-line platinum-based chemoimmunotherapy have limited effective treatment options and poor prognosis. This study evaluated the efficacy and safety of ivonescimab combined with liposomal irinotecan in this setting. Methods: This phase 2, multicenter, single-arm trial enrolled SCLC pts who progressed during or after platinum-based chemoimmunotherapy. Eligible pts were required to be ≥18 years of age and have an ECOG PS of 0 or 1. Pts received ivonescimab (20 mg/kg, IV, Q3W) plus liposomal irinotecan (56.5 mg/m², IV, Q2W) until disease progression or unacceptable toxicity. The primary endpoint was 6-month progression-free survival (PFS) rate (ClinicalTrials.gov: NCT06478043). Results: Between October 22, 2024 and August 27, 2025, 60 pts were included in the intention-to-treat population. Median age was 62.0 years (range: 38-75), 56 (93.3%) were male, and 53 (88.3%) had ECOG PS 1. At baseline, 35.0% and 26.7% of pts had liver and brain metastases, respectively. A total of 63.3% of pts had a chemotherapy-free interval of more than 90 days. As of December 15, 2025, with a median follow-up time of 7.3 months (95% CI: 6.0-9.0), the 6-month PFS rate was 72.0% (95% CI: 57.0-82.6). Median PFS was 9.8 months (95% CI: 6.7-13.4), and median OS was not reached. The confirmed objective response rate was 61.7% (95% CI: 48.2-73.9; all partial responses) and the disease control rate was 91.7% (95% CI: 81.6-97.2). In subgroup analysis, the median PFS was 11.9 months (95% CI: 7.3-NE) for patients with a CFI ≥90 days and 7.0 months (95% CI: 4.4-NE) for those with a CFI < 90 days. Treatment-related adverse events (TRAEs) of grade ≥3 occurred in 16 pts (26.7%). The most common grade ≥3 TRAEs were decreased neutrophil count (8.3%), decreased white blood cell count (8.3%), fatigue (6.7%), and diarrhea (3.3%). TRAEs led to treatment interruption in 31.7% and chemotherapy dose reduction in 25.0% of pts. No patient discontinued all treatment drugs due to TRAEs; discontinuation of ivonescimab alone occurred in 6 pts (10%). Immune-related AEs occurred in 33.3 % of pts, with grade 3 events in 8.3%. No grade ≥4 irAEs or treatment-related deaths were reported. Conclusions: Ivonescimab combined with liposomal irinotecan demonstrated encouraging antitumor activity with a manageable safety profile as a second-line treatment for SCLC pts after platinum-based chemoimmunotherapy. These results support further investigation in randomized controlled trials. Clinical trial information: NCT06478043 .