On April 12, 2021 Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, reported initiation of its Phase 1/2 FORGE-1 study of TPX-0131, a potent inhibitor of the anaplastic lymphoma kinase (ALK) and multiple resistant mutations of ALK (Press release, Turning Point Therapeutics, APR 12, 2021, View Source [SID1234577924]).

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The investigational new drug (IND) application for TPX-0131 is Turning Point’s third IND to be cleared by the FDA in less than 2 years, and FORGE-1 is the company’s fourth clinical study to initiate during the same period of time.

The study was initiated in Australia, with U.S. site activations now planned.

"With a lack of available therapies to address a broad spectrum of ALK resistant mutations, we are encouraged by the preclinical potency for TPX-0131, particularly against the G1202R solvent front mutation which is reported to occur in more than 40% of biopsies with resistance mutations," said Ben Solomon, M.D., principal investigator for the FORGE-1 study, a medical oncologist and group leader of the Molecular Therapeutics and Biomarkers Laboratory at the Peter MacCallum Cancer Centre in Melbourne, Australia. "In addition, TPX-0131 has been shown preclinically to penetrate the central nervous system, which is important in the treatment of patients with ALK-positive non-small cell lung cancer as the disease often progresses in the brain."

ALK alterations are estimated to be responsible for 3% to 5% of non-small cell lung cancer (NSCLC) cases annually in the U.S. and EU5 countries. In preclinical studies, TPX-0131 potently inhibits wildtype ALK and is more potent in comparison to approved ALK inhibitors against many clinically observed resistance mutations, including the G1202R solvent front mutation, L1196M gatekeeper mutation, and multiple compound mutations. In addition, TPX-0131 has shown brain tissue penetration after repeat oral dosing.

"Our clinical study of TPX-0131 will begin with a Phase 1 dose finding portion in patients previously treated with up to 2 prior ALK tyrosine kinase inhibitors, a population we believe is underserved today by available therapies that are less potent against known resistant mutations of ALK," said Mohammad Hirmand, M.D., chief medical officer of Turning Point Therapeutics.

The Phase 1 dose finding portion of the FORGE-1 study will enroll patients with locally advanced or metastatic TKI-pretreated ALK-positive NSCLC. Patients with up to 2 prior ALK TKIs and 1 prior platinum-based chemotherapy will be enrolled. The study endpoints include safety and tolerability, determination of the maximum tolerated dose and/or the recommended Phase 2 dose, and objective response rate by RECIST 1.1.