TPS11592 Background: Epithelioid hemangioendothelioma (EHE) is an ultra-rare vascular sarcoma with about 120 cases diagnosed in the US per year. Although it is commonly considered an indolent disease, in its aggressive form clinical outcomes are poor. Molecularly, EHE is characterized by the presence of oncogenic fusions with HIPPO pathway effectors TAZ or YAP; TAZ-CAMTA1 or YAP-TFE3. YAP/TAZ are modulators of mTORC1 in preclinical models, suggesting that mTOR inhibition may be an effective treatment mechanism for EHE. Nab-sirolimus is albumin bound sirolimus, which achieves higher intratumoral accumulation compared to oral sirolimus and has demonstrated increased antitumor activity in preclinical cancer models compared to the oral mTOR inhibitors sirolimus and everolimus. This is an open label, multi-center, single arm, phase II clinical trial with a two-stage design, testing nab-sirolimus for progressing or symptomatic EHE. The primary objective is to determine ORR of nab-sirolimus in patients with EHE who require systemic treatment. We hypothesize that nab-sirolimus will have significant clinical efficacy for EHE as measured by the primary endpoint of objective response rate, as well as by secondary outcomes including progression free survival benefit over historical controls and by improvement in patient reported outcomes (PROs). If positive, this trial could lead to a new standard of care for treating EHE. Methods: This is a single arm, multi-center, phase 2 study with a two-stage design. Key inclusion criteria include histologically or cytologically confirmed EHE that is either progressing or clinically symptomatic, not a candidate for curative intent surgery, and requires systemic therapy in the opinion of the investigator, radiographically evaluable disease by RECIST v1.1, age ≥18 years, ECOG performance status ≤ 2, and adequate end organ function. With a Simon two-stage optimal design with one sided alpha 0.10, power 90%, assuming a historical control ORR 5% to detect an ORR of 20% (alternative hypothesis), 12 patients will be included in the first stage. If there is ≥ 1 response, an additional 25 patients will be enrolled to a total of 37 patients. ≥ 4 responses are needed for a significant result. The total planned accrual is 41 patients to account for unevaluable patients who may be enrolled, 10% above the required evaluable patients. Planned post hoc subgroup analyses will include outcomes by fusion type and presence of serosal effusions at the time of study enrollment. The trial is registered at clinicaltrials.gov NCT07104331. Clinical trial information: NCT07104331 .
Wagner et al. (Thu,) studied this question.