Abstract 74P
Background
ABM-1310 is a novel small molecule BRAF-selective inhibitor with high cellular permeability and brain penetration. Here we report the final result from a phase 1 study of ABM-1310 in pts with solid tumors (Clinical trial information: NCT05501912).
Methods
This is a multi-center, open-label, dose-escalation with cohort expansion phase 1 study. In the dose-escalation part, pts received ABM-1310 at either 150 or 200mg bid. Dose-limiting toxicities (DLT) were assessed by a “3+3 design”. Primary objectives were maximum tolerated dose (MTD), safety and tolerability of ABM-1310. Secondary objectives included pharmacokinetics (PK) and anti-tumor activity.
Results
Between September 2022 to June 2024, 20 pts (10 male; median age 59 years) were treated with ABM-1310: 8 pts received 150mg bid, 12 pts were on 200mg bid regimens. For safety evaluation, all 20-pts experienced at least once treatment-related adverse events (TRAEs). Grade 1-2 TRAEs account for 75% of cases. The two most common TRAEs were asymptomatic electrocardiogram QT prolongation (AQTP, n=13) and rash (n=10). Five pts had ≥Grade 3 TRAE including AQTP, dyspnea, lipase increased, direct bilirubin increased and unknow death. Two treatment-related SAE were dyspnea and unknown death. There were no DLT events. For anti-tumor activity, among all 19 efficacy-evaluable pts, 10 of them had partial response (PR), objective response rate (ORR) 52.6%, including ORR 57.1% in 7 pts with NSCLC, ORR 37.5% in 8 pts with CRC. The overall disease control rate was 94.7%. 7 patients remained in PR condition when the study ended, 4 of them DoR >6 months (range from 7.3 to 15 months). The MTD for ABM-1310 was determined at 200mg bid. Both ABM-1310 150mg bid and 200mg bid regimens were further tested in the expansion cohorts. The PK assessment of ABM-1310 blood exposure vs. dosage showed a linear dose-proportional relationship.
Conclusions
ABM-1310 was generally well tolerated without unknown safety concerns. ABM-1310 monotherapy’s anti-tumor activity was clearly observed in pts with BRAF V600 mutation-positive solid tumors, especially in pts with NSCLC and CRC.
Clinical trial identification
NCT05501912.
Editorial acknowledgement
Legal entity responsible for the study
ABM Therapeutics.
Funding
ABM Therapeutics.
Disclosure
J. Li: Non-Financial Interests, Personal, Member: ASCO, CSCO. Y. Cheng: Financial Interests, Personal, Member: Jilin Cancer Hospital. Y. Fu, Z. Yang, C. Chen, Z. Yang: Financial Interests, Personal, Member: ABM Therapeutics. All other authors have declared no conflicts of interest.