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.

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/m2 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 .