1927P - AL2846 in patients (pts) with radioiodine-refractory differentiated thyroid carcinoma (RR-DTC) previously treated with tyrosine kinase inhibitors (TKI): Preliminary clinical results from the phase Ib study

Background

Approximately 15% of metastatic DTC will become RR, with a substantial impact on its prognosis. Although the majority of pts with RR-DTC initially achieve disease control with TKI, most will eventually develop treatment resistance and disease progression. AL2846, a multikinase inhibitor, mediate tumor growth and angiogenesis inluding VEGFR, AxL, c-MET, may lead to improved efficacy of pts with RR-DTC treated with prior TKI.

Methods

This multi-center, open-label, phase Ib study enrolled RR-DTC pts treaed with prior TKI therapy. Eligible pts received oral 90mg or 120mg 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 31 Mar 2024, total 28 pts (90mg, n=17; 120mg, n=11) were enrolled in this study, with 27 pts (96%) remaining on treatment. 20 pts were papillary carcinoma, 8 pts were follicular carcinoma. All pts had progressed following 1 or 2 prior VEGFR-targeted therapy, about 22% patients received 2 lines of prior therapy. Among the 28 pts, 21 were efficacy evaluable, 7 have not reached the first evaluation. 2 pts achieved partial response (PR), while 19 pts had stable disease (SD) at best response, 11 pts had SD more than 16 weeks. DCR was 100% (21/21). The most common (>20%) treatment-emergent adverse events (TEAE) included AST/ALT increased, hypocalcemia, hypertension, elevated lactic dehydrogenase (LDH), hypercholesterolemia, hand-foot syndrome (HFS). TEAE ≥ grade 3 occurred in 5% of pts, only 1 patient had serious adverse event (SAE) of nephrotic syndrome. 4 pts led to dose reduction of AL2846 mainly due to HFS, proteinuria and oral mucositis. Interestingly, 1 patient achieved tumor shrinkage after dose-upregulation to 120mg during treatment, and was well tolerated.

Conclusions

AL2846 demonstrated a well-tolerated safety profile and a promising antitumor activity in previously TKI treated RR-DTC pts, which warrants further clinical evaluation.

Clinical trial identification

NCT05745363.

Editorial acknowledgement

Legal entity responsible for the study

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Funding

Chia Tai Tianqing Pharmaceutical Group Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.