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