NEW YORK – Aadi Bioscience on Thursday said it has begun dosing patients in a Phase II tumor-agnostic registrational trial of its mTOR inhibitor Fyarro (nab-sirolimus), dubbed PRECISION 1.
The study will involve approximately 120 patients age 12 and older with solid tumors characterized by TSC1 and TSC2 inactivating mutations. The open-label trial will have two arms: one for 60 patients with TSC1-mutated tumors and a second for another 60 patients with TSC2 mutations. The endpoints of interest in the trial are efficacy, safety, and tolerability.
Fyarro is already approved in the US for advanced malignant perivascular epithelioid cell tumors (PEComa), a rare type of sarcoma commonly associated with TSC1 and TSC2 mutations. Those genes are part of the PI3K/Akt/mTOR signaling pathway, which is often activated in tumors.
The Los Angeles-based firm previously collected data within a program that expanded access to Fyarro for patients with malignancies other than malignant PEComa. At the American Society of Clinical Oncology's annual meeting last year, Aadi reported that five out of eight patients with refractory tumors and TSC1/2 inactivating mutations partially responded to Fyarro. Most of these patients had never tried an mTOR inhibitor.
After discussing the activity seen in this program with the US Food and Drug Administration, Aadi decided to advance Fyarro into a tissue-agnostic "basket trial" involving patients with TSC1/2-mutated solid tumors. The FDA has granted fast-track designation to Fyarro in this setting. Aadi anticipates reporting preliminary data from PRECISION 1 in the first half of 2023.
Aadi previously reported results from the Phase II AMPECT trial of Fyarro in locally advanced or metastatic malignant PEComa, which showed an overall response rate of 39 percent, with two out of 31 patients achieving a complete response. After 36 months of follow-up, the median duration of response had not yet been reached.
Similar to the adverse events seen with other mTOR pathway inhibitors, in Aadi's trials Fyarro-treated patients had stomatitis, myelosuppression, infection, hypokalemia, hyperglycemia, interstitial lung disease, hemorrhage, and hypersensitivity reactions.