A phase I clinical trial of ABP1019A monotherapy in patients with advanced malignant solid tumors.

e15147 Background: ABP1019A is an innovative tyrosine kinase inhibitor (TKI) that effectively inhibits EGFR, FGFR1-4, VEGFR1-3, RET, PDGFR-α, and CSF-1R. Importantly, it exhibits broader superior inhibitory activity compared to Lenvatinib and Regorafenib. In vivo efficacy tests in nude mice showed that it had good safety and high inhibitory effect on more than a dozen of tumors such as glioma, pancreatic, lung, esophageal, colorectal, liver, thyroid cancer. Moreover, the small molecular ABP1019A has high blood-brain barrier permeability, which is good for ABP1019A to treat some tumors in brain. The phase I trial had been conducted in patients with 7 types of advanced malignant solid tumors. Methods: The study enrolled patients with 7 types of different advanced malignant solid tumors in the dose escalation study, and all of patients had undergone 2~5 lines of systemic therapy. In order to evaluate the DLT and safety, PK characteristics and preliminary efficacy of ABP1019A, the dose was increased from 10 mg qd and bid, 30 mg qd, 40md qd, and 50 mg qd by the traditional 3+3 mode with continuous medication. Results: As of Feb. 2025, 11 patients with advanced solid tumors were enrolled in the dose escalation study, including 1 patient of 10 mg qd and bid, 3 patients of 30 mg qd, 3 patients of 40 mg qd, and 2 patients of 50 mg qd. The PK results showed that the dose was linearly correlated with exposure, and its T 1/2 was about 15-30 hours. 7 of 11 patients had completed one or more efficacy evaluation after 6 weeks of treatment, among which 5 of 7 patients were observed as reduced SD (all of 3 patients in the dose 40 mg group: 1 pancreatic cancer, 1 glioma, 1 lung squamous carcinoma, and 2 of 3 patients in the dose 30 mg group: 1 thyroid cancer, 1 rectal cancer), 2 patients were PD. Moreover, for a patient of pancreatic cancer with two lesions in the tail of pancreas (39.1mm) and liver (24.2mm), its first efficacy evaluation was totally reduced tumor burden -23.7%, and its third efficacy evaluation was totally reduced tumor burden -31.9% (PR), so the pancreatic cancer was well controlled after taking 40 mg qd for 18 weeks. During the dose escalation study, no DLT occurred from 10 mg qd to 50 mg qd, and all of 3 patients with pancreatic and other cancers in the dose 40 mg group showed good safety, tolerability and high efficacy. The dosing regimen was adjustable between 30 mg and 40 mg qd according to the patient weight, tolerance and severity of AEs during the continuous medication period. Conclusions: The results of ABP1019A in phase I dose escalation study showed that this monotherapy was well tolerated, and had preliminary anti-tumor efficacy on advanced pancreatic cancer, glioma, lung and thyroid cancer, etc. A phase II exploratory study is ongoing to further verify the safety and anti-tumor efficacy of ABP1019A on 8 types of tumors including glioma, pancreatic cancer, osteosarcoma, cholangiocarcinoma, SCLC, colorectal cancer, esophageal cancer, and gastric cancer. Clinical trial information: ChiCTR2400081035 .