ABI-009 (nab-sirolimus) in advanced malignant perivascular epithelioid cell tumors (PEComa): Preliminary efficacy, safety, and mutational status from AMPECT, an open label phase II registration trial.

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11005 Background: Malignant PEComa is a rare, aggressive sarcoma, with no approved treatment or prior clinical trials. Case reports suggest mTOR activation through mutations or deletions of TSC1 or TSC2 and activity of mTOR inhibitors in this disease. ABI-009 is an albumin-bound mTOR inhibitor with increased tumor uptake. The AMPECT trial is the first prospective study in malignant PEComa. Methods: Eligible patients (pts) with centrally confirmed PEComa receive ABI-009 (100 mg/m2 IV, wkly, 2/3 wks) until progression or unacceptable toxicity. Primary endpoint: ORR by independent review (IR), assessed every 6 wks (RECIST v1.1). Secondary endpoints: duration of response (DOR), PFS6, PFS, and safety. Exploratory endpoints (EE): investigator-assessed (IA) outcomes and mutational status. Sample size: 30 efficacy-evaluable pts based on target ORR of 30% (primary analysis planned when all pts treated ≥6 mo). Results: EE and safety are reported (IR pending). As of Feb 12, 2019, enrollment is complete; 34 pts treated, 31 evaluable for efficacy, 42% (13/31) pts ongoing Rx. IA ORR is 42% PR (13/31, 95% CI: 24.5, 60.9), 35% SD (11/31), and 23% PD (7/31); 69% of PRs were reached at 1st restaging (wk 6); 69% PRs are ongoing, with 5 pts >1yr and 2 pt >2 yrs on Rx (all ongoing). Other IA outcomes: median DOR is not reached; PFS6 is 66%; median PFS is 8.9 mo (95% CI: 5.5, -). The most common (>30%) nonhematologic treatment-related AEs (TRAEs) of any grade: mucositis (65%), fatigue (53%), nausea/weight loss (35% each), diarrhea (32%); the most common (>15%) hematologic TRAEs: anemia (44%) and thrombocytopenia (18%). Pneumonitis (15%) was G1/G2. The most common (>10%) G3 TRAEs: mucositis (18%), anemia (12%); No grade ≥4 TRAEs. TSC1 or TSC2 mutations occurred in 5 and 9 (no overlap) of 25 pts with known mutational status, respectively. PR was seen in 100% (9/9) pts with TSC2 mutation, 20% (1/5) pts with TSC1 mutation, and 9% (1/11) pts without mutation in TSC1 or TSC2, P < 0.0001 (2x3 Fisher exact test). PR was significantly higher in pts with TSC2 mutations vs pts without mutation in TSC1 or TSC2, P = 0.0001 (Fisher exact test). Disease control (PR+SD) was seen in 93% (13/14) pts with TSC1 or TSC2 mutations vs 55% (6/11) pts without mutation in TSC1 or TSC2, P = NS. Conclusions: Preliminary IA outcomes showed that ABI-009 treatment of PEComa resulted in substantial and durable responses with manageable toxicities. TSC2 mutations were associated with IA response. Clinical trial information: NCT02494570.