453MO - A phase I study for safety, tolerability, pharmacokinetics, and anti-tumor activity of ABM-1310 in patients (pts) with BRAF V600 mutated recurrent primary brain tumours: Interim result

Background

ABM-1310 is a high blood brain barrier penetrant BRAF inhibitor. Here we report the interim result from a phase I study of ABM-1310 in pts with recurrent primary brain tumors (Clinical trial information: NCT05892653).

Methods

This is an open-label, dose-escalation with cohort expansion 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

As of April 8, 2024, 15 pts (7 male; median age 39 years) have been treated. Eight received 150mg bid, 7 were on 200mg bid of ABM-1310. For safety, all pts experienced treatment-related adverse events (TRAEs). Two most common TRAEs were asymptomatic QT prolongation (n=11) and rash (n=8). Grade 1-2 TRAEs accounts for 88.7% of cases. Seven pts had Grade 3 ECG QT prolongation. There was only one pt who was in the 150mg bid dose group discontinued earlier due to asymptomatic Grade 3 QT prolongation. In the 200mg bid dose group, 3 pts each needed either treatment withholding or a dose reduction, respectively. There were no DLT events, no Grade 4 AE, no SAE and no treatment-related deaths. For anti-tumor activity, among 13 efficacy evaluable pts, 3 pts had partial response (PR, includes glioblastoma [GBM], WHO Grade 2 and 3 each of pleomorphic xanthoastrocytoma) and 8 pts had stable disease as their best response. Two pts maintained a PR response for > 8 months and continue study treatment to date. The MTD for ABM-1310 was 200mg bid. The regimen of ABM-1310 150mg bid was chosen for the expansion cohorts. Preliminary PK assessment of ABM-1310 blood exposure vs. dosage showed a linear dose-proportional relationship. The trial is ongoing.

Conclusions

ABM-1310 was generally tolerated without unknown safety signals. Preliminary anti-tumor activity was observed in pts with BRAF V600-mutated recurrent primary brain tumors.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

ABM.

Funding

ABM.

Disclosure

All authors have declared no conflicts of interest.