FDA Approves Nab-Sirolimus for Locally Advanced Unresectable or Metastatic PEComa

The FDA approved nab-sirolimus as the first drug specifically indicated for the treatment of patients with malignant perivascular epithelioid cell tumors.

The FDA approved sirolimus albumin-bound nanoparticles for injectable suspension (nab-sirolimus; Fyarro) for intravenous use in the treatment of patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumors (PEComa), according to a press release from drug maker Aadi Biosciences.1

The regulatory decision was based on findings from the registration phase 2 AMPECT study (NCT02494570) in which nab-sirolimus monotherapy was administered to patients with advanced malignant PEComa (n = 31). A total of 2 patients had achieved a complete response out of 12 total responders (39%) identified by independent review after prolonged follow-up. Patients have not reached a median duration of response after 36 months. For patients who were responders, 92% had a response that lasted more than 6 months, 67% had a response lasting more than 12 months, and 58% had a response lasting more than 2 years.

“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,” Andrew Wagner, MD, PhD, a senior oncologist at Dana-Farber Cancer Institute and the principal investigator in the pivotal AMPECT registrational trial, said in the press release.

Nab-sirolimus is a nanoparticle albumin-bound mTOR inhibitor that has yielded significantly higher levels of tumor accumulation, mTOR target suppression, and anti-tumor activity.

Results from the trial were presented at the 2020 American Society of Clinical Oncology Annual Meeting, during which investigators reported an overall response rate (ORR) of 39% (95% CI, 22%-58%), which was the primary end point.2 At the time of that assessment in 31 evaluable patients, 1 achieved a complete response and 11 achieved partial responses. Additionally, 52% had stable disease rate and 10% of progressive disease. At 12 weeks or more, the disease control rate was 71%. The investigation was the first prospective study in advanced malignant PEComa. 

A total of 34 patients received intravenous nab-sirolimus at 100 mg/m2 weekly for 2 to 3 weeks until progression or unacceptable toxicity. 

Secondary end points included the progression-free survival (PFS) rate at 6 months, PFS, and overall survival. At the time of the primary analysis, all patients had been treated for 6 months or more.

At 6-months, the PFS was 71% (95% CI, 47.7%-85.1%). A total of 67% of patients had responded to treatment by the first post-baseline scan during week 6. Patients also had a median time to response of 1.4 months (95% CI, 1.3-2.8). 

In more than 10% of patients, grade 3 non-hematologic events occurred that included stomatitis, rash, fatigue, and infections. Grade 3 laboratory abnormalities included worsened lymphocytopenia from baseline, increased glucose, and decreased potassium.

Nab-sirolimus was previously granted priority review for this indication in August 2021.3 This approval comes ahead of the Prescription Drug User Fee Act target date set by the FDA of November 26, 2021.


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://yhoo.it/3nIwPn6

2. Wagner AJ, Ravi V, Riedel RF, et al. Long-term follow-up for duration of response (DoR) after weekly nab-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): results from a registrational open-label phase II trial, AMPECT. J Clin Oncol. 2020;38(suppl 15):11516. doi:10.1200/JCO.2020.38.15_suppl.11516

3. Aadi Bioscience announces FDA acceptance and priority review for the new drug application of FYARRO™ for the treatment of advanced malignant PEComa. News release. Aadi Bioscience Inc. July 26, 2021. Accessed October 19, 2021.