A phase IIa clinical trial of ABP1011T monotherapy in patients with advanced malignant solid tumors.

Abstract

e15145 Background: ABP1011 T is an innovative tyrosine kinase inhibitor (TKI) that effectively inhibits EGFR, c-MET, FGFR1-4, VEGFR1-3, RET, and c-KIT. Importantly, it exhibits broader superior inhibitory activity compared to Lenvatinib and Regorafenib. In the completed clinical phase I trial, 12 types of tumors had been investigated, and its DCR was 61.5%. The PK results showed that the dose was linearly correlated with exposure in the phase I study, and its t 1/2 was about 14 hours. One case of DLT was observed in the 16mg bid dose group, and the accumulation factor of 2 to 4 for bid dosing, so the RP2d was 20mg qd. The clinical Phase IIa trial is ongoing in patients with 9 types of advanced malignant solid tumors (such as sarcoma, small cell lung cancer (SCLC), pancreatic, colorectal, cervical, esophageal, and neuroendocrine tumors, etc.) to evaluate the safety, tolerability and broad-spectrum efficacy of ABP1011T. Methods: This is an open-label, multi-center studies. The study enrolled patients with advanced malignant solid tumors such as SCLC, sarcoma, squamous lung cancer, pancreatic cancer, cervical cancer, squamous esophageal cancer (EC), bladder cancer (BC), colorectal cancer, etc., by using the basket design method, and to perform continuous administration of 20 mg qd (≥60 kg) or 16 mg qd ( < 60 kg), to preliminarily assess the efficacy of ABP1011T tablets in patients with the targeted advanced solid tumors, and to evaluate the safety and tolerability of the continuous dosing. Results: By the end of Dec. 2024, 45 subjects with nine types of advanced solid tumors (who had failed standard treatment) were enrolled, and 37 of 45 subjects had completed at least 1 tumor evaluation after 6 weeks of drug administration, including 1 CR, 5 PR, and 25 SD, with an ORR of 16.2% and overall DCR of 83.8% (RECISIT 1.1). There were 6 cases of SCLC (ORR 33.3%), 6 cases of osteosarcoma (ORR 16.7%), 4 cases of cervical cancer (ORR 25%), 2 cases of bladder cancer (ORR 50%), 3 cases of esophageal cancer, and 3 cases of squamous lung cancer. Moreover, all the aforementioned tumors exhibited a 100% disease control rate (DCR), with a notable trend toward continued tumor reduction as treatment progressed. The median duration of treatment was 5.7 (2-11) cycles. The most common (grade ≥3) TRAEs included hypertension (22%), with the rest being less than 5%, which could be effectively controlled by taking antihypertensive drugs; and 14 SAEs (16 instances) related to the IIa trial, with an incidence rate of 31%, accounting for 5.3% of all TRAEs. Conclusions: The results of ABP1011T in Phase IIa exploratory study showed that ABP1011T was well tolerated, and its mono-therapy showed varying degrees of tumor shrinkage in advanced sarcoma , SCLC, EC, BC, and cervical cancer that had been treated with Anlotinib and PD-1, etc. A phase IIb study of ABP1011T will be conducted to further validate the safety, tolerability and efficacy in advanced malignant solid tumors. Clinical trial information: ChiCTR2400088650 .