Background
Phase II single-arm open-label AMPECT, nab-sirolimus (ABI-009; nanoparticle albumin-bound sirolimus, mTORC1 inhibitor) in locally advanced unresectable or metastatic malignant PEComa. N=31 evaluable, sites USA/Europe/Australia. PEComa: ultra-rare mesenchymal tumour with near-universal mTOR pathway activation (TSC1/TSC2 mutations or TFE3 fusions). NCT02494570; data cutoff December 2020.
Interventions and follow up
Treatment: Nab-sirolimus (ABI-009) 100 mg/m² IV days 1 and 8 of each 21-day cycle until progression or intolerance (PEComa)
Primary endpoint: ORR (confirmed PR+CR by RECIST 1.1, blinded independent central review)
mFollow up: 21.3 mo
Primary endpoint: ORR (confirmed PR+CR by RECIST 1.1, blinded independent central review)
mFollow up: 21.3 mo
Results
ORR (n=31 evaluable): 39% (12 confirmed: 1 CR, 11 PRs)
SD rate: 39%
DCR: 77%
mDOR: not reached (range 3.7–30.9+ mo)
mPFS: 8.7 mo (95% CI 5.6–not reached)
mOS: not reached at cutoff
By biomarker: TSC1/TSC2-mutated (n=20) ORR 50%; TSC-wildtype / TFE3-rearranged (n=11) ORR 18%
SD rate: 39%
DCR: 77%
mDOR: not reached (range 3.7–30.9+ mo)
mPFS: 8.7 mo (95% CI 5.6–not reached)
mOS: not reached at cutoff
By biomarker: TSC1/TSC2-mutated (n=20) ORR 50%; TSC-wildtype / TFE3-rearranged (n=11) ORR 18%
Adverse events
Grade ≥3 AEs: 58%
Most common any-grade: mucositis/stomatitis 71%, fatigue 55%, nausea 39%, hyperglycemia 32%, anemia 26%, thrombocytopenia 26%
Grade ≥3 specific: thrombocytopenia 19%, fatigue 13%, mucositis 10%, hyperglycemia 10%
Pneumonitis: any-grade 10%, grade ≥3 3%
Discontinuation due to AEs: 13%
Most common any-grade: mucositis/stomatitis 71%, fatigue 55%, nausea 39%, hyperglycemia 32%, anemia 26%, thrombocytopenia 26%
Grade ≥3 specific: thrombocytopenia 19%, fatigue 13%, mucositis 10%, hyperglycemia 10%
Pneumonitis: any-grade 10%, grade ≥3 3%
Discontinuation due to AEs: 13%
Conclusions
Nab-sirolimus achieved 39% ORR with 77% DCR and durable responses in malignant PEComa (mPFS 8.7 mo). Highest ORR (50%) seen in TSC1/TSC2-mutated patients, consistent with mTOR-driven biology. Established mTORC1 inhibition as the first evidence-based systemic therapy for malignant PEComa.
Key Limitations
Small single-arm N=31, no comparator; ultra-rare disease limits accrual; ORR surrogate with immature OS; benefit concentrated in TSC1/TSC2-mutant subgroup (n=20); high grade ≥3 toxicity (58%).
Clinical Context
FDA-approved Nov 2021 for advanced malignant PEComa — first and only approved therapy for this indication. ESMO recognizes mTOR inhibition as standard for advanced PEComa; TSC1/TSC2 mutation testing informs expected benefit.