66MO - Intravenous sirolimus (albumin bound, SRL-HSA) in malignant perivascular epithelioid cell tumors (PEComas): A multicenter, open label, phase Ib trial

Background

Malignant PEComes is a rare aggressive soft tissue tumor, with few approved treatments in China. SRL-HSA is a novel intravenous sirolimus (albumin bound). This study aimed to evaluate the safety and efficacy of SRL-HSA in patients with malignant PEComas.

Methods

This study consisted of two parts, dose escalation and PK expansion (part 1) and dose expansion (part 2). Eligible patients were histologically confirmed advanced soft tissue sarcoma (STS) including malignant PEComas (part 1), recurrent or metastatic malignant PEComas without previous mTOR inhibitor treatment (part 2). In part 1, rolling-six design was used to examine three dose levels (50, 85 and 100 mg/m²). In part 2, 100 mg/m² of SRL-HSA was administered intravenously on day 1 and day 8 of 21-day cycle. The primary endpoint was safety and recommended phase III dose (RP3D) (part 1), and objective response rate (ORR) (part 2).

Results

As of December 9, 2024, 44 patients were enrolled (n=26 for part 1, and n=18 for part 2) with 2 STS and 42 PEComas. The median age was 50.5 years (range 23-71). 27.3% of patients had ≥ 3 metastatic organs. The most common primary site was uterus. 7 (15.9%) patients had previous treatment with mTOR inhibitors (all in part 1). No dose-limiting toxicities occurred. 42 (95.5%) patients experienced treatment related adverse events (TRAEs), which 14 (31.8%) were ≥grade 3. The common ≥grade 3 TRAEs (≥5%) was hypertriglyceridemia (5/44). The RP3D was 100 mg/m². 41 patients with PEComas were evaluable for efficacy. The confirmed ORR was 34.1% with 1 CR and 13 PRs. The disease control rate (DCR) was 65.9%. Among 34 evaluable patients with no prior mTOR inhibitors treatment, the confirmed ORR and DCR were 41.2% (95%CI 24.7-59.3) and 67.6% (95%CI 49.5-82.6). The median time to response was 1.51 (IQR 1.35, 2.79) months. The median duration of response (DOR) was not reached, 15-month DOR rate was 100%. The median progression free survival (PFS) was not reached, 12-month PFS rate was 65.4%.

Conclusions

SRL-HSA is effective and well tolerated in the treatment of malignant PEComas, supporting phase III study to further explore the efficacy of SRL-HSA in patients with malignant PEComas.

Clinical trial identification

NCT05625919.

Editorial acknowledgement

Legal entity responsible for the study

CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd.

Funding

CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co. Ltd.

Disclosure

C. Li, J. Hao, Y. Xin, X. Wan, X. Zhang, J. Yang: Financial Interests, Personal, Full or part-time Employment: CSPC Zhongqi Pharmaceutical Technology (Shijiazhuang) Co., Ltd. All other authors have declared no conflicts of interest.