NEW YORK – Nested Therapeutics said Thursday that it will begin evaluating its investigational agent NST-628 in patients with advanced solid tumors harboring genetic alterations in the MAPK pathway.
The US Food and Drug Administration cleared Nested's investigational new drug application to start clinical trials of NST-628, which the firm calls a pan-RAF/MEK molecular glue targeting RAF and MEK nodes in the RAS-MAPK pathway.
Cambridge, Massachusetts-based Nested expects to begin dosing patients with NST-628 in its Phase I study during the first half of this year. The study will include a dose escalation portion followed by a dose expansion portion, and is expected to include 230 patients total.
In the first part of the trial, Nested will enroll patients with any advanced solid tumor harboring a genetic alteration in, or evidence of tumor dependence upon, the RAS/MAPK pathway. In the second part of the trial, the firm is enrolling patients into several histology-specific cohorts, including melanoma patients with activating NRAS mutations or select BRAF alterations; patients with solid tumors harboring NRAS activating mutations; patients with solid tumors harboring KRAS-activating mutations; patients with solid tumors harboring select BRAF alterations; and patients with glioma harboring BRAF alterations.
Patients must experience disease progression following standard of care or be ineligible for other treatment options to be eligible for the trial. Nested will primarily be studying the agent's safety and tolerability, though the firm also plans to measure objective response rates, progression-free survival, overall survival, and the agent's pharmacokinetics.
Nested believes that NST-628 has a potential advantage over other drugs targeting the MAPK pathway since it has a superior therapeutic index and can prevent pathway reactivation, Nested Chief Medical Officer Philip Komarnitsky noted in a statement.