Surufatinib monotherapy or combined with vinorelbine as a late-line therapy in patients with refractory advanced non–small cell lung cancer (NSCLC).

e20543 Background: Surufatinib (S, a small-molecule inhibitor of VEGFR1-3, FGFR1 and CSF-1R) has shown synergy mechanism with vinorelbine (V) in lung cancer cell lines (A549 cells and PC9 cells) and nude mice experiment. Here, we evaluated the efficacy and safety of surufatinib with or without vinorelbine in refractory advanced NSCLC patients (pts). Methods: This single center, open label, phase Ⅱ study (NCT04922658) has two cohorts. Eligible pts with stage IIIb/IV NSCLC who progressed after at least two lines of previous therapies were assigned to cohort 1 (S, 250 mg qd, po, q3w plus V, 20 mg, po, once every 2 days, q3w) or cohort 2 (S, 300mg qd, po, q3w). Treatment continued until disease progression, intolerable toxicity, or study withdrawal. Primary endpoint was PFS. Secondary endpoints included ORR, DCR, OS, and safety. Results: Up to Jan 15, 2024, 17 pts were enrolled in cohort 1 (median age 62 years, male 76.47%, TNM stage IV 70.59%, ECOG PS 1 94.12%). 32 pts were assigned to cohort 2 (median age 55 years, male 65.62%, TNM stage IV 87.5%, 71.88% pts failing with at least three lines of previous therapies). In cohort 1, 12 pts had received at least one post-baseline tumor assessment (evaluable), among which ORR was 16.7%, DCR was 100 %. 75% pts had stable or shrinking tumors (based on best of response). Median PFS was not reached in cohort 1. In cohort 2, 32 pts were evaluable, ORR was 3.1%, DCR was 87.5%. 62.5% pts had stable or shrinking tumors. Median PFS was 5.4m (95% CI 3.4, 7.4). In subgroup analysis, compared with pts with distant metastases (mainly bone, liver, and brain metastases), pts without above metastases showed significantly longer PFS (6.9m vs 4.1m, p = 0.0071). Additionally, PFS was significantly prolonged in pts who were anti-angiogenic drugs naïve, in contrast with those who received anti-angiogenic therapies before (8.3m vs 4.1m, p = 0.004). Similar result was observed in pts with enlargement tumors versus stable or shrinking tumors (2.8m vs 6.9m, p<0.0001). Longer PFS was observed in pts with squamous NSCLC (sq vs non-sq, 8.3m vs 4.1m, p = 0.0655) or those who received two lines of previous therapies vs at least three lines (6.2m vs 4.8m, p = 0.0728). The most common treatment-emergent adverse events (Total, Grade≥3) in cohort 1 were proteinuria (25.0%, 0), hypothyroidism (16.67%, 0), and diarrhea (8.33%, 8.33%). The most common adverse events (Total, Grade≥3) in cohort 2 were proteinuria (50.0%, 14.7%), hypothyroidism (44.1%, 0), and hypoproteinemia (35.3%, 5.9%). Conclusions: Surufatinib, or combined with vinorelbine, showed encouraging survival benefits and promising anti-tumor activity with acceptable toxicity in the late-line treatment of refractory advanced NSCLC, especially in patients without distant metastases, never using anti-angiogenic drugs, or with squamous NSCLC. The results warrant further investigations in a large cohort. Clinical trial information: NCT04922658 .