A metabolic gene methylthioadenosine phosphorylase (MTAP) deletion is present in about 15% of all cancers. The open-label clinical trial (NCT03435250) will include up to 54 patients to test AG-270, a methionine adenosyltransferase 2a (MAT2A) inhibitor.
The study is designed to evaluate the safety and clinical activity of AG-270, as well as how the therapy candidate acts in the body and how it affects patients with advanced solid tumors or with lymphoma with MTAP deletions.
The therapy will be orally administered as a single agent once a day in cycles of 28 days. The trial’s first part is a dose-escalation study to determine the maximum tolerated or optimal dose of AG-270 in a certain number of patients.
The second part of the study is designed as a dose-expansion phase, in which AG-270 is given to additional patients at the maximum tolerated or optimal dose to continue evaluating its safety, tolerability, and clinical activity in future studies.
To be eligible to enroll, patients must demonstrate loss of the MTAP protein in their tumors or show a lack of the CDKN2A tumor suppressor gene, which is usually absent when the MTAP gene is deleted. Additional eligibility information is available here.
“In addition to significant milestones for our late-stage portfolio this year, we are pleased to demonstrate the continued productivity of our research engine by advancing our sixth internally discovered molecule into the clinic,” Scott Biller, MD, chief scientific officer of Agios, said in a press release.
“As a first-in-class MAT2A inhibitor, AG-270 has the potential to benefit the large number of patients whose cancer is characterized by the loss of MTAP. We look forward to conducting the early clinical work that will explore the pharmacology and clinical activity of MAT2A inhibition in tumors carrying this deletion,” he said.
The Phase 1 study follows the presentation of preclinical data demonstrating how small molecule inhibitors of MAT2A were effective in MTAP-deleted tumor xenograft models, which use patients’ own cancer tissue to test new experimental medicines.
The data was presented at the 2017 Keystone Tumor Metabolism meeting, which took place in March last year.
The study is being conducted in partnership with Sarah Cannon, a clinical trial and research institution.
AG-270 stems from a collaborative agreement established in 2016 with Celgene. The agreement was established after Agios found that MAT2A belongs to a key pathway in MTAP-deleted tumors. When this protein is blocked, it leads to potent anti-tumor activity.