Vilzemetkib

Pancreatic cancer patients urgently need new treatments, and we explored the efficacy and safety of combination therapy with AL2846 and gemcitabine in pancreatic cancer patients. This was a single-arm, single-center, open-label phase I/IIa study (NCT06278493). The dose-escalation phase was designed to evaluate the maximum tolerated dose (MTD) of AL2846 combined with gemcitabine. One or two dose levels were chosen for the dose-expansion phase. Treatment continued until disease progression, intolerable toxicity, patient withdrawal, or at the investigators' discretion. The primary study endpoint is to evaluate the safety and MTD of AL2846 combined with gemcitabine. The secondary endpoints included objective response rate (ORR), progression-free survival (PFS), overall survival (OS), and disease control rate (DCR). Between August 2018 and July 2021, 33 pancreatic cancer patients were enrolled in the study. A total of 15 patients were enrolled in the dose-escalation phase, and the MTD was not determined. Eventually 90 mg and 120 mg of AL2846 were chosen for the dose-expansion phase, in which 11 patients (90 mg) and 7 patients (120 mg) were administered. Treatment-related adverse events (TRAEs) of any grade were reported in 30 (90.91%) patients, and those of grade ≥ 3 were reported in 16 (48.48%) patients. The most frequently reported grade ≥ 3 TRAEs were thrombocytopenia (18.18%), neutropenia (12.12%), elevated γ-glutamyltransferase (6.06%), proteinuria (6.06%), and gastrointestinal hemorrhage (6.06%).The ORR was 6.06%, and the DCR was 72.73%. The median PFS was 3.71 months (95% CI: 3.38-4.11), and the median OS was 5.59 months (95% CI: 4.11-8.71). Gemcitabine and Al2846 combination therapy exhibited tolerable safety, but there was no improvement in efficacy over standard treatment. Further evaluation of this approach is still needed.

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.

This multi-center, open-label, phase Ib study enrolled patients with RR-DTC treated with prior tyrosine kinase inhibitor (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.

From February 16, 2023 to March 13, 2025, 33 patients (90 mg, n = 21; 120 mg, n = 12) were enrolled in this study. All patients had disease progressed following one or two prior VEGFR-targeted therapy. The median age was 59 years (47, 63), and 17 (51.5%) patients were female. The ORR was 12.12%, with two 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% confidence interval (CI), 10.97–not estimable], 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 (TRAE) included aspartate aminotransferase/alanine aminotransferase 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.

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