FDA Approves Nab-Sirolimus for Advanced Malignant PEComa


FDA approval has been granted to nab-sirolimus for intravenous use as treatment of patients with advanced malignant perivascular epithelioid cell tumors.

The FDA has approved nab-sirolimus (Fyarro), a nanoparticle albumin-bound mTOR inhibitor, sirolimus albumin-bound nanoparticles for intravenous use as treatment of patients with advanced malignant perivascular epithelioid cell tumors (PEComa), according to a press release by Aadi Bioscience, Inc.1

“The approval of Fyarro, the first approved drug for advanced malignant PEComa, an aggressive sarcoma with a poor prognosis and few treatment options, will provide physicians with a new weapon for treating patients with this rare disease,” said Andrew Wagner, MD, PhD, a senior oncologist at Dana-Farber Cancer Institute and the principal investigator in the pivotal AMPECT registrational trial. “In our AMPECT trial, Fyarro demonstrated durable responses in mTOR inhibitor-naïve patients with locally advanced unresectable or metastatic PEComa, with an acceptable and manageable safety profile. This is a drug that will be welcomed by the physician community as the only approved therapeutic option for patients with advanced malignant PEComa.”

The approval is based on results from the phase 2 AMPECT clinical trial (NCT02494570), which looked at the agent in this patient population. The single-group assignment study has an actual enrollment of 34 participants. The primary end point is objective response rate (ORR). Secondary end points include duration of response (DoR), progression-free survival (PFS) up to 32 months, overall survival (OS), and the number of participants with adverse events (AEs).

During the study, all patients received the experimental agent.

The analysis, which was published in the Journal of Clinical Oncology in 2020, included 21 patients. The ORR was 39% (95% CI, 22%-58%). Stable disease was seen in 52% of patients while 10% had progressive disease. In patients with metastatic disease, the ORR was 46% (95% CI, 26.6%-66.6%). The median DoR observed at the 1-year follow-up was 25.8 months (range, 5.6-42.4+). The median PFS was 8.9 months (95% CI, 5.5 to not reached). At 2 months, the PFS was 78.5% (95% CI, 58.5%-89.9%), at 6 months the PFS rate lowered to 69.5% (95% CI, 47.6%-83.7%), and the 12-month PFS was 45.4% (95% CI, 22.6-65.7%). OS was not reached. At 6 months, OS was 93.2% (95% CI, 75.5%-98.3%), and 88.8% at 12-months (95% CI, 68.7%-96.3%).

No grade 4 treatment-related AEs were observed. Pneumonitis occurred in 18% of patients. Grade 2 anemia and grade 1 cystitis caused 6% of patients with discontinue treatment.

In order to participate in the study, patients must have had a confirmed PEComa, have 1 or more measurable lesions, have an ECOG score of 0 or 1, and a life expectancy greater than 3 months. Patients with uncontrolled or symptomatic central nervous system metastases, have active gastrointestinal bleeding, a preexisting thyroid abnormality, or uncontrolled diabetes were not eligible to participate.2

“Patients living with locally advanced or metastatic PEComa are in urgent need of new treatment options. The approval of Fyarro is a significant advancement for treating patients with this disease. Treating sarcoma patients in my practice, I have seen the need for a therapy that addresses the specific molecular alterations of advanced malignant PEComa. I am encouraged that Fyarro provided a clinically meaningful benefit in overall response rate, with some patients responding for up to several years. I am pleased to have FYARRO as a new therapeutic option to offer my advanced malignant PEComa patients, said Robert G. Maki, MD, PhD, clinical director of the Sarcoma Program, and professor of Medicine at the University of Pennsylvania, in the press release.


1. Aadi Bioscience announces FDA approval of its first product FYARRO™ for patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa). News release. Aadi Bioscience. November 23, 2021. Accessed November 23, 2021. https://bit.ly/3oNbzMg

2. A phase 2 study of ABI-009 in patients with advanced malignant PEComa (AMPECT). ClinicalTrials.gov. Accessed September 8, 2021. https://bit.ly/2

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