(P 167) STUDY-END ANALYSIS FROM AMPECT, AN OPEN-LABEL, PHASE 2 REGISTRATION TRIAL OF PATIENTS WITH ADVANCED MALIGNANT PECOMA TREATED WITH nab-SIROLIMUS, SHOWING DURABILITY OF RESPONSE AND LONG-TERM SAFETY

Objective: Malignant perivascular epithelioid cell tumor (PEComa) is an aggressive, rare sarcoma in which cytotoxic chemotherapies have limited patient benefit. nab-Sirolimus is a mechanistic target of rapamycin inhibitor (mTORi) that utilizes albumin-bound nanoparticle technology. In pre-clinical animal models, treatment with nab-sirolimus resulted in significantly higher tumor uptake, mTOR target suppression, and tumor suppression, with a distinct pharmacokinetic profile, relative to oral mTORi’s. nab-Sirolimus is approved in the US for the treatment of adult patients with locally advanced unresectable or metastatic malignant perivascular epithelioid cell tumor (PEComa) based on the primary analysis results of the AMPECT trial (Wagner et al. J Clin Oncol. 2021). Both the primary analysis results and an updated analysis from AMPECT were previously reported; however, the median duration of response (DOR) was not reached at that time. Here, we report the analysis of AMPECT data through study completion (April 29, 2022), including median DOR.

Methods: The AMPECT trial was an open-label, multicenter Phase 2 registration study in mTORi-naïve adult patients (≥18 years) with histologically confirmed diagnosis of malignant PEComa and Eastern Cooperative Oncology Group performance status score of ≤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 objective response rate (ORR) by independent radiology review. Secondary endpoints included DOR, progression-free survival (PFS), overall survival (OS), and safety.

Results: A total of 34 patients were treated with nab-sirolimus in the study (safety-evaluable); 31 patients were efficacy-evaluable. A large majority of patients were female (82%, 25/31) and had metastatic disease (85%, 26/31); median age at baseline was 60 years (range, 27–78). Among the 31 efficacy-evaluable patients, ORR at AMPECT study completion was 39% (95% confidence interval: 21.8, 57.8). The best overall response was complete response in 2/31 (7%) patients, partial response in 10/31 (32%) patients, stable disease in 16/31 (52%) patients, and progressive disease in 3/31 (10%) patients. Median DOR was 39.7 months. Median PFS remained at 10.6 months; median OS was 53.1 months. There were no new or unexpected safety signals and no grade 4 or 5 treatment-related adverse events (TRAEs) throughout the study. The most common non-hematologic TRAEs were stomatitis (28/34 [82%]) and fatigue and rash (21/34 [62%] each). The most common hematologic TRAEs were anemia (18/34 [53%]) and thrombocytopenia (12/34 [35%]). Non-infectious pneumonitis occurred in 7/34 (21%) patients and was Grade 1 or 2 in all cases.

Conclusion: The AMPECT study met its primary endpoint, and had a median DOR of over 3 years. ORR, PFS, and OS at study completion, and the DOR of over 3 years highlight the clinical benefit of nab-sirolimus in the treatment of this aggressive, rare sarcoma. The safety profile indicates that nab-sirolimus is tolerable for long-term treatment, without unexpected AEs or new safety signals at study closure.