AL2846, a novel multi-kinase inhibitor, for previously treated radioiodine-refractory differentiated thyroid cancer: Exploratory clinical results from the phase Ib study.

[PURPOSE] This exploratory phase Ib study aimed to evaluate the efficacy and safety of AL2846, a multi-kinase inhibitor, in patients with radioiodine-refractory differentiated thyroid cancer (RR-DTC) following disease progression on prior VEGFR-targeted therapy.

[PATIENTS AND METHODS] This multi-center, open-label, phase Ib study enrolled RR-DTC patients treated with prior TKI therapy. Eligible patients received oral 90 mg or 120 mg of AL2846 capsules, once daily. The primary endpoint was objective response rate (ORR). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS) and safety.

[RESULTS] From 16 Feb 2023 to 13 Mar 2025, 33 patients (90 mg, n=21; 120 mg, n=12) were enrolled in this study. All patients had disease progressed following 1 or 2 prior VEGFR-targeted therapy. The median age was 59 (47, 63), 17 patients (51.5%) were female. The ORR was 12.12%, with 2 partial responses observed in each dose group. The DCR was 100% in the 90 mg group and 91.67% in the 120 mg group, respectively. The median PFS in 90 mg was 18.33 months (95% CI: 10.97, NE), with a 6-month PFS rate of 94.4% and a 12-month PFS rate of 70.8%. The most common treatment-related adverse events (TRAEs) included AST/ALT increased, hypertension, proteinuria, hypocalcemia and hand-foot syndrome. Grade ≥3 TRAEs occurred in 47.62% of patients in the 90 mg group and 41.67% in the 120 mg group.

[CONCLUSIONS] AL2846 showed an acceptable safety profile and a promising antitumor activity in previously TKI treated RR-DTC patients, with 90 mg has a more favorable effect.