ABM-1310 is a novel small molecule BRAF inhibitor that has shown promising anti-cancer activity and a good safety profile across a variety of advanced BRAF V600-mutant solid tumors.
The FDA has granted an orphan drug designation (ODD) to ABM-1310 for the treatment of patients with glioblastoma (GBM) harboring a BRAF V600 mutation, according to ABM Therapeutics, Inc.1
ABM-1310 is a novel small molecule BRAF inhibitor that is orally administered. The product has high BRAF-mutation selectivity, high water solubility, and high blood-brain barrier permeability, and is currently being developed by ABM Therapeutics, Inc. Multiple phase 1 studies are ongoing, evaluating ABM-1310 across clinical sites in the United States and China in patients with BRAF V600-mutant advanced solid tumors.
Interim findings from a phase 1 study presented at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023 showed ABM-1310 to have promising anticancer activity and a good safety profile when used for the treatment of patients with advanced BRAF V600-mutant solid tumors. This included in patients with primary brain tumors, such as GBM and other gliomas.2
In the multicenter, open-label, dose-escalation trial, patients with BRAF V600-mutated solid tumors were enrolled and assessed to determine the primary end point of maximum tolerated dose and recommended phase 2 dose of ABM-1310 with or without cobimetinib (Cotellic), along with secondary end points of safety, tolerability, pharmacokinetics, and preliminary efficacy.
Findings revealed that as of November 28, 2022, 20 patients with a median age of 57.5 years were enrolled and treated with ABM-1310 monotherapy across 6 dose levels in part A of the study. Sixteen patients in part A were efficacy evaluable and among them, 2 had a partial response (PR) and 8 had stable disease (SD) as their best response.
Among patients, 100% experienced adverse events (AEs), with the most frequent being skin rash (40%) and QT prolongation (20%). Drug-related grade ≥3 AEs occurred in 3 patients and consisted of nausea/vomiting, QT prolongation and rash, and 2 patients had drug-related serious AEs, including nausea/vomiting and creatinine increase.
In part B of the study, ABM-1310 in combination with cobimetinib was assessed at 2 dose levels, 100 mg twice a day (n = 3) and 200 mg twice a day (n = 3). Four patients had AEs and drug-related AEs, including rash and QT prolongation, and no SAEs were reported. Of the 3 evaluable patients, 1 patient with melanoma had a PR and 1 had SD as their best response.
No DLTs were confirmed in either dose-escalation part of the trial and no patients discontinued treatment prematurely for any safety or tolerability reason. Additionally, no drug-related deaths were reported.
Overall, ABM-1310 at doses up to 200 mg twice a day, either alone with cobimetinib, was generally well tolerated, with no new safety signals. This trial is ongoing.
Additionally, a new phase 1 clinical trial taking place in China has been initiated, specifically evaluating ABM-1310 to target GBM.
Brain Cancer Awareness Month: Challenges and Innovations in Treatment
May 13th 2024In an interview with Targeted Oncology for Brain Cancer Awareness Month, Theodore Schwartz, MD, discussed the challenges of targeting brain tumors, emerging therapies, and strategies to overcome the blood-brain barrier.
Read More
Olaptesed Pegol Wins FDA Fast Track Designation in Brain Cancer
April 3rd 2024The FDA granted a fast track designation to olaptesed pegol with bevacizumab and radiotherapy for patients with newly diagnosed glioblastoma that is resistant to chemotherapy and where measurable tumor remains after surgery.
Read More
TTFields Increases Time to Progression in Patients With Brain Metastases From NSCLC
March 27th 2024Findings from the phase 3 METIS trial found that tumor-treating fields were able to significantly improve time to intracranial progression in patients with brain metastases from non-small cell lung cancer.
Read More