Reference Detail

Ref Type

abstract

PMID

Authors

W. Li, Z. Kang, S. Li, F. Chen, B. Zhang, M. Huang, Z. Yang, C. Chen, Z. Yang

Title

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

Journal	Vol	Issue	Date	Pages	Journal Short Title
Annals of Oncology	35	Supplement 2	September 2024

URL

https://www.annalsofoncology.org/article/S0923-7534(24)02042-8/fulltext

Abstract Text

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.

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Molecular Profile	Treatment Approach

Gene Name	Source	Synonyms	Protein Domains	Gene Description	Gene Role

Therapy Name	Drugs	Efficacy Evidence	Clinical Trials

Drug Name	Trade Name	Synonyms	Drug Classes	Drug Description

Gene	Variant	Impact	Protein Effect	Variant Description	Associated with drug Resistance

Molecular Profile	Indication/Tumor Type	Response Type	Therapy Name	Approval Status	Evidence Type	Efficacy Evidence	References
BRAF V600X	brain cancer	predicted - sensitive	ABM-1310	Phase I	Actionable	In a Phase I trial, ABM-1310 treatment was well tolerated and resulted in preliminary antitumor activity with 3 partial responses and 8 stable disease among 13 patients with brain tumors harboring BRAF V600 mutations, including a partial response in a patient with glioblastoma and 2 partial responses in patients with pleomorphic xanthoastrocytoma (Ann Oncol (2024) 35 (suppl_2): S411; NCT05892653).	detail...