Long-term follow-up for duration of response (DoR) after weekly <i>nab</i>-sirolimus in patients with advanced malignant perivascular epithelioid cell tumors (PEComa): Results from a registrational open-label phase II trial, AMPECT.
Andrew J. Wagner, Vinod Ravi, Richard F. Riedel, Kristen N. Ganjoo, Brian Andrew Van Tine, Rashmi Chugh, Lee D. Cranmer, Erlinda M. Gordon, Jason L. Hornick, David J. Kwiatkowski, Heng Du, Berta Grigorian, Anita N. Schmid, Shihe Hou, Katherine E. Harris, Neil Desai, Mark A. Dickson
Abstract
11516 Background: Malignant PEComa is a rare, aggressive sarcoma, with no approved medical treatment. Cytotoxic chemotherapies have limited benefit for patients with advanced disease. The AMPECT trial measured the effects of nab-sirolimus (ABI-009) and is the first prospective study in advanced malignant PEComa. nab-Sirolimus is a nanoparticle albumin-bound mTOR inhibitor with significantly higher intratumoral drug levels, mTOR target suppression, and anti-tumor activity in animal models versus other mTOR inhibitors. This report presents long-term follow-up of DoR after the primary analysis. Methods: Patients (N=34) received nab-sirolimus (100mg/m 2 IV, weekly, 2/3 weeks) until progression or unacceptable toxicity. Primary endpoint: ORR by IRR. Key secondary endpoints included DoR, PFS6, OS, and safety. Exploratory endpoints included correlation of tumor genotype and outcome. The sample size of 30 efficacy-evaluable patients was based on an estimated ORR of 30% and the lower bound of the 95%CI of ORR to exclude values less than 14.7%. The primary analysis was conducted when all patients were treated ≥6 months (May 22, 2019). This report updates the primary response analysis and DoR with an additional 8.5-month of follow-up. Results: As of Feb 06, 2020, of the 31 efficacy-evaluable patients, the confirmed ORR by IRR was 39% (12/31, 95%CI: 21.8, 57.8), with 1 complete response (CR) and 11 partial responses (PR), 52% stable disease (SD, 16/31, with 10/16 SD ≥12 weeks), and 10% progressive disease (3/31); the disease control rate (CR+PR+SD ≥12 weeks) was 71%. PFS6 was 71% (95%CI: 47.7, 85.1). The majority of responses (67%) were reached at the first post-baseline scan at week 6, with a median time to response of 1.4 months (95%CI: 1.3 to 2.8). The median DoR by IRR was not yet reached (range 5.6-38.7+ months; calculated median 22.2+ months) with 8/12 (67%) responders still on treatment for >1 year and 5/12 (42%) >2 years. Mutational analysis available for 25 patients identified that TSC2 loss-of-function mutations significantly correlated with response; 8/9 (89%) patients with TSC2 had a confirmed response. Conclusions: Responses of advanced malignant PEComa to nab-sirolimus were highly durable and occurred in 39% of patients based on independent review. The high disease control rate with manageable toxicities suggest that nab-sirolimus is effective and represents an important new treatment option for these patients. NCT02494570. Clinical trial information: NCT02494570 .