Abstract B010: Response to treatment with <i>nab</i>-sirolimus among patients with primary uterine tumors: A subgroup analysis from AMPECT
Authors: Vinod Ravi, Mark A. Dickson, Kristin Ganjoo, Li Ding, Anita N. Schmid, Norma A. Palma, Willis H. Navarro, Andrew J. Wagner
Journal: Clinical Cancer Research (2024)

Abstract Introduction/objective: AMPECT (NCT02494570) is a pivotal study of nab-sirolimus in patients with malignant perivascular epithelioid cell tumors (PEComa). Malignant PEComa is an aggressive, rare sarcoma for which cytotoxic chemotherapies provide limited patient benefit. Inactivation of TSC1 or TSC2 tumor suppressor genes, upstream of mTORC1, is commonly associated with malignant PEComa; these mutations occurred in 56% of patients in AMPECT. nab-Sirolimus is an mTOR inhibitor (mTORi) that utilizes albumin-bound nanoparticle technology to drive higher intratumoral drug levels and more complete pathway suppression than conventional mTORis. nab-Sirolimus is approved in the USA for the treatment of advanced or metastatic malignant PEComa based on the primary analysis results of the AMPECT trial, which showed a confirmed overall response rate (ORR) of 39%, regardless of mutation status. We describe outcomes of a subset of patients with primary uterine PEComa, representing 23% of efficacy-evaluable patients in AMPECT. Methods: AMPECT was an open-label, multicenter, phase 2 registration study in mTORi-naïve adult patients (≥18 years old) with a histologically confirmed diagnosis of malignant PEComa and Eastern Cooperative Oncology Group performance status score ≤1. Patients received nab-sirolimus 100 mg/m2 intravenously on days 1 and 8 of a 21-day cycle until progression or unacceptable toxicity. The primary endpoint was ORR by independent radiology review. Key secondary endpoints included time to response, duration of response (DOR), and safety. Results: A total of 7 patients with uterine PEComa were treated with nab-sirolimus in AMPECT and were evaluable for both safety and efficacy. Mean ± SD age was 60.0 ± 13.4 years, and 71% (5/7) of patients were White. ORR was 43% (3/7 patients); all 3 were confirmed partial responses and were seen in patients with tumors with somatic inactivating alterations in TSC1 or TSC2. Two (29%) patients had best response of stable disease. For the 3 responders, time to response was 1.4, 1.4, and 1.5 months, and DOR was 5.6, 36.0+, and 39.7 months. All 7 patients had ≥1 treatment-related adverse event (TRAE; grade 3, 43%); no grade ≥4 or serious TRAEs occurred. Conclusions: Rates of response to treatment and safety findings in patients with primary uterine PEComa treated with nab-sirolimus in AMPECT were consistent with those previously reported in the overall patient population. Responses were rapid and durable. Notably, all responders had TSC1 or TSC2 alterations; however, there were too few patients in this subset to draw conclusions regarding efficacy in tumors without these alterations. nab-Sirolimus is being further evaluated in a tumor-agnostic trial of patients with TSC1 or TSC2 inactivating alterations (PRECISION I; NCT05103358). Citation Format: Vinod Ravi, Mark A. Dickson, Kristin Ganjoo, Li Ding, Anita N. Schmid, Norma A. Palma, Willis H. Navarro, Andrew J. Wagner. Response to treatment with nab-sirolimus among patients with primary uterine tumors: A subgroup analysis from AMPECT [abstract]. In: Proceedings of the AACR Special Conference on Endometrial Cancer: Transforming Care through Science; 2023 Nov 16-18; Boston, Massachusetts. Philadelphia (PA): AACR; Clin Cancer Res 2024;30(5_Suppl):Abstract nr B010.