Efficacy and biomarker exploration of anlotinib plus penpulimab in second-line ES-SCLC: Results from the phase 2 ALTER-L041 trial.

Zeng, Liang; Tian, Fang; Wang, Cunji; Chen, Qun; Jiang, Wenjuan; Liang, Juan; Tan, Yanming; Yan, Huan et al. · Cell Rep Med · 2026

prospective_cohort · Level II

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Abstract

Treatment options are limited for patients with extensive-stage small cell lung cancer (ES-SCLC) after platinum-based therapy. This open-label, single-arm, multicenter phase 2 trial evaluates penpulimab plus anlotinib in 65 patients with first-line platinum-resistant ES-SCLC. The confirmed objective response rate by blinded independent central review is 41.5% (95% confidence interval [CI]: 29.2%-53.8%), and the disease control rate is 75.4% (95% CI: 64.6%-86.1%). Median progression-free survival and overall survival are 4.4 (95% CI: 3.5-5.3) and 10.5 (95% CI: 4.1-17.2) months, respectively. Grade ≥3 treatment-related adverse events occurred in 23.1% of patients, with no new safety signals. Exploratory circulating tumor DNA (ctDNA) analysis suggests that lower baseline maximum somatic allele frequency is associated with improved survival, and decreased T cell receptor clonal diversity is observed at disease progression. Penpulimab plus anlotinib shows promising antitumor activity with a manageable safety profile and may represent a potential second-line treatment option for platinum-resistant ES-SCLC. This study was registered at ClinicalTrials.gov (NCT05001971).