ABM-1310 Receives FDA Fast Track Designation for BRAF V600E+ Glioblastoma

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The FDA has granted fast track designation to ABM-1310 for the treatment of patients with glioblastoma harboring BRAF V600E mutations.

FDA

The FDA has granted fast track designation to ABM-1310 for the treatment of patients with glioblastoma harboring BRAF V600E mutations, according to an announcement from ABM Therapeutics.¹

“We are very grateful to the FDA for recognizing the potential of our novel next-generation investigational drug ABM-1310 to help patients with brain tumors,” Zane Yang, MD, chief medical officer of ABM Therapeutics, stated in a news release. “This offers ABM an interactive collaboration with the FDA to ensure ABM-1310 clinical development expeditiously with the highest standards of safety and quality.”

In August 2023, the FDA granted orphan drug designation to ABM-1310 for the treatment of patients with BRAF V600E–mutated glioblastoma.²

The novel, small-molecule BRAF inhibitor is currently under investigation in phase 1 trials in the United States (NCT04190628) and China (NCT05501912; NCT05892653).

Data from the first-in-human study being conducted in the United States were presented at the 2023 ASCO Annual Meeting.³ Among patients treated with ABM-1310 monotherapy who were evaluable for efficacy in part A (n = 20), partial responses (PRs) were observed in 1 patient with glioblastoma, 1 with thyroid cancer, and 1 with xanthoastrocytoma. Additionally, 9 patients experienced stable disease (SD) per RECIST v1.1 or Response Assessment in Neuro-Oncology criteria.

Among evaluable patients treated with ABM-1310 plus cobimetinib (Cotellic) in part B (n = 8), 1 patient with melanoma and 1 patient with thyroid cancer achieved a PR, and 2 other patients experienced SD.

Among patients evaluable for safety in part A (n = 21), 15 experienced treatment-related adverse effects (TRAEs). Four patients had grade 3 TRAEs consisting of nausea/vomiting (n = 1), QT prolongation (n = 2), and rash (n = 1). Serious TRAEs occurred in 2 patients, which included grade 3 nausea/vomiting (n = 1) and grade 2 increased creatinine (n = 1).

In part B (n = 8), 7 patients experienced any-grade TRAEs, including 1 patient who had grade 3 rash.

All 3 patients in part A treated with 250 mg of ABM-1310 monotherapy experienced dose-limiting toxicities leading to dose interruption or reduction, including grade 3 QT prolongation (n = 1), grade 2 QT prolongation (n = 1), and grade 2 increased creatinine plus grade 3 QT prolongation (n = 1). Notably, no patients discontinued treatment early due to safety or tolerability, and no treatment-related deaths were reported.

The open-label, dose-escalation trial is enrolling adult patients with advanced or recurrent BRAF-mutated solid tumors. Those with brain metastases from solid tumors for primary malignant brain tumors are allowed to enroll, and prior treatment with BRAF/MEK inhibitors is permitted.

In part A, patients received oral ABM-1310 twice per day at doses of 25 mg (n = 3), 50 mg (n = 3), 100 mg (n = 4), 150 mg (n = 4), 200 mg (n = 4), and 250 mg (n = 3). In part B, patients were treated with 100 mg of ABM-1310 twice per day plus 60 mg of cobimetinib once per day (n = 3) or 200 mg of ABM-1310 twice per day plus 60 mg of cobimetinib once per day (n = 5).

The primary objectives of the study are to determine the maximum tolerated dose and recommended phase 2 dose of ABM-1310, and secondary objective included safety/tolerability, preliminary efficacy, and pharmacokinetics.

References

ABM Therapeutics’ ABM-1310 granted fast track designation by the FDA following orphan drug designation. News release. September 26, 2023. Accessed September 26, 2023. http://www.abmtx.com/site/newsdetails/88
US FDA grants orphan drug designation to ABM-1310 for the treatment of patients with glioblastoma harboring BRAF V600 mutation. News release. ABM Therapeutics. August 2, 2023. Accessed September 26, 2023. http://www.abmtx.com/site/newsdetails/85
Piha-Paul SA, Nagpal S, Weise AM, et al. A phase 1, multicenter, open-label study of a new BRAF inhibitor ABM-1310 in adult patients (pts) with BRAFv600-mutated solid tumors. J Clin Oncol. 2023;41(suppl 16):3098. doi:10.1200/JCO.2023.41.16_suppl.3098