Gemcitabine + nab-sirolimus (albumin-bound mTOR inhibitor) delivers 30% ORR in advanced LMS with TSC1/2 alterations

Gemcitabine (antimetabolite chemotherapy) was combined with nab-sirolimus (nab-S; nanoparticle albumin-bound sirolimus, an IV mTORC1 inhibitor designed for higher intratumoral exposure) in an investigator-initiated, single-center Phase I BOIN dose-escalation study in advanced leiomyosarcoma (n=12; 7 uterine; median age 55). The MTD was gemcitabine 900mg/m² + nab-S 100mg/m² on Days 1 and 15 every 28 days; 1/9 patients at DL2 had a cycle-1 DLT (grade 3 mucositis/diarrhea), the most common grade 3–4 TRAE was thrombocytopenia, and 1 patient discontinued after grade 3 gemcitabine-attributed pneumonitis. Among 10 response-evaluable patients, ORR was 30% (3/10) with 90% clinical benefit; median PFS was 8.38 months (95% CI 1.68–NR) with 6-month PFS 58%—numerically above typical later-line benchmarks like pazopanib (median PFS ~4.6 months in PALETTE) and trabectedin vs dacarbazine in LPS/LMS (median PFS ~4.2 months).