An Open-Label, Single-Arm, Phase II Trial of Sintilimab Plus Anlotinib for Metastatic Non-Small Cell Lung Cancer After First-Line PD-(L)1 Inhibitor

Abstract

Background: Although immune checkpoint inhibitors (ICIs) have markedly improved first-line management of non-small cell lung cancer (NSCLC), many tumors eventually escape control after anti-PD-(L)1 therapy, leaving a clear therapeutic gap. Preclinical studies and preliminary clinical data suggest that coupling ICIs with anti-angiogenesis therapy can yield complementary antitumor effects. Consequently, we launched this investigation to evaluate the therapeutic benefit and tolerability of sintilimab, a PD-(L)1–blocking monoclonal antibody, together with the oral multi-target anti-angiogenesis agent anlotinib in metastatic NSCLC individuals experiencing progression after first-line PD-(L)1 inhibition. Methods: At Zhejiang Cancer Hospital, we conducted a phase II trial, single-arm, open-label investigation (registration No. NCT04691388). Patients were adults diagnosed with metastatic NSCLC whose disease had advanced after PD-(L)1 blockade; they received sintilimab plus anlotinib on a 21-day cycle. Investigator-assessed objective response rate (ORR) served as the principal efficacy endpoint. Results: Between March 2021 and January 2024, twenty-nine individuals were recruited (median age 63, range 45–74, 96.6% male). Tumor assessment identified five partial responses (PR) (17.2%), nineteen cases of stable disease (SD) (65.5%) and three progressions (10.3%), yielding an ORR of 17.2% and a disease-control rate (DCR) of 82.8%. The cohort's median progression-free survival (PFS) measured 5.0 months (90% CI, 4.2–7.3), and 41.1% of participants remained progression-free at six months. Overall survival reached a median of 15.1 months (90% CI, 8.6–not yet reached), with an 18-month survival proportion of 44.8%. Grade ≥ 3 treatment-related toxicity was dominated by hypertension, occurring in 10.3% of participants; no patient discontinued therapy or died because of drug-related events. Conclusion: Sintilimab combined with anlotinib exhibited favorable antitumor activity and tolerable toxicity in post-anti-PD-(L)1 therapy of metastatic NSCLC patients, supporting further randomized controlled trials. Trial Registration: ClinicalTrials.gov: NCT04691388. Registered December 31, 2020.