Reference Detail

Ref Type

Abstract

PMID

Authors

Sarina A. Piha-Paul, Seema Nagpal, Amy M. Weise, Fadi S. Braiteh, Chen Chen, Charles Qing Huang, William Liu, Yong Hu, Zane Yang, Katy K. Tsai

Title

A phase 1, multicenter, open-label study of a new BRAF inhibitor ABM-1310 in adult patients (pts) with BRAFv600-mutated solid tumors.

Journal	Vol	Issue	Date	Pages	Journal Short Title
Journal of Clinical Oncology	41	16_Suppl	June 1, 2023

URL

https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.3098

Abstract Text

Background: ABM-1310 is a novel small-molecule BRAF inhibitor with high water solubility, cell permeability, and blood-brain barrier penetration as demonstrated in preclinical studies. Here we report preliminary findings from a first-in-patient phase 1 study of ABM-1310. Methods: This US multicenter, open-label, dose-escalation with cohort expansion trial includes adult pts with advanced BRAFv600-mutated solid tumors, including those with active brain metastasis from solid tumors or primary malignant brain tumors. Previous BRAF/MEK inhibitor treatment is permitted. In dose escalation Part A, ABM-1310 monotherapy is given orally twice a day (25–250 mg bid). In dose escalation Part B, ABM-1310 (100 and 200 mg bid) is given in combination with the MEK inhibitor cobimetinib (60 mg QD d1–21 q4w). Primary objectives: determine maximum tolerated dose and recommended phase 2 dose of ABM-1310 ± cobimetinib. Secondary objectives: safety/tolerability; pharmacokinetics; preliminary efficacy. Dose-limiting toxicities (DLTs) are assessed during cycle 1 by a 3+3 design. Results: As of November 28, 2022, 20 pts (65% male; median age 57.5 years) have been treated with ABM-1310 monotherapy across six dose levels in Part A: 25 mg bid (n=3); 50 mg bid (n=3); 100 mg bid (n=4); 150 mg bid (n=4); 200 mg bid (n=4); 250 mg bid (n=2). All pts experienced adverse events (AEs), most frequently skin rash (40%) and QT prolongation (20%). Three pts had drug-related grade ≥3 AEs (nausea/vomiting, QT prolongation and rash) and two had drug-related serious AEs (SAEs) (nausea/vomiting and creatinine increase). Among 16 efficacy evaluable pts, two (pleomorphic xanthoastrocytoma and glioblastoma) had a partial response (PR) and eight had stable disease (SD) as their best response (per RECIST or RANO). In Part B, two ABM-1310 dose levels were assessed in combination with cobimetinib: 100 mg bid (n=3) and 200 mg bid (n=3). Four pts had AEs and drug-related AEs (rash and QT prolongation). There were no SAEs. Among three evaluable pts, one (melanoma) had a PR and one had SD as their best response. There were no confirmed DLTs in either dose-escalation Part A or B, although a few pts had ABM-1310 treatment interruption and subsequent dose reduction. No pts discontinued prematurely for any safety or tolerability reason and there were no drug-related deaths. Preliminary assessment of ABM-1310 drug exposure vs dosage showed a linear dose-proportional relationship. This trial is ongoing. Conclusions: ABM-1310 at the currently tested doses up to 200 mg bid, either alone or in combination with cobimetinib, was generally well tolerated, with no new safety signals. Preliminary efficacy data demonstrate favorable activity of ABM-1310 in pts with BRAFv600-mutated solid tumors, including primary CNS tumors, and pts previously refractory to other BRAF/MEK inhibitors and I/O therapies. Clinical trial information: NCT04190628

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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	Advanced Solid Tumor	predicted - sensitive	ABM-1310	Phase I	Actionable	In a Phase I trial, ABM-1310 treatment was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 2 partial responses (1 pleomorphic xanthroastrocytoma, 1 glioblastoma) and 8 stable diseases among 16 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628).	detail...
BRAF V600X	melanoma	predicted - sensitive	ABM-1310 + Cobimetinib	Case Reports/Case Series	Actionable	In a Phase I trial, the combination of ABM-1310 and Cotellic (cobimetinib) was tolerated and demonstrated preliminary efficacy in patients with advanced solid tumors harboring BRAF V600X, resulting in 1 partial response in a patient with melanoma and 1 stable disease among 3 evaluable patients (J Clin Oncol 41, 2023 (suppl 16; abstr 3098); NCT04190628).	detail...