Investigator-initiated phase II trial of ABSK043, an oral PD-L1 inhibitor, in patients with angiogenic sarcoma.

Abstract

TPS11593 Background: Angiogenic sarcomas (AS) represent a group of rare mesenchymal malignancies arising from the vascular endothelium. Patients with locally advanced or metastatic disease have poor outcomes due to limited availability of effective systemic treatment options. Emerging data suggest that immune checkpoint blockade (ICB) has activity in select patients, but prospective data is lacking for ultra-rare subtypes of AS including intimal sarcoma and epithelioid hemangioendothelioma (EHE). Methods: This is a single institution phase II investigator-initiated open label trial of ABSK043, an oral PD-L1 inhibitor in patients with AS. The primary endpoint is objective response rate. Secondary endpoints include progression free survival, overall survival and incidence of treatment emergent adverse events. Exploratory objectives include tissue- and blood-based correlative analyses to identify molecular biomarkers associated with ICB response/resistance in AS. Key inclusion criteria include histologically proven EHE, intimal sarcoma or scalp angiosarcoma with evidence of disease progression, age ≥18 years, ECOG performance status 0-2, adequate organ function, and measurable disease by RECIST v1.1. Exclusion criteria include ongoing systemic immunosuppressive therapy, active autoimmune disease, prior treatment with PD-(L)1 directed therapy, untreated brain metastases, or gastrointestinal conditions that may impair oral drug absorption. Participants will receive ABSK043 800mg orally twice daily until disease progression or unacceptable toxicity. Radiologic assessments by CT or MRI will be performed every 12 weeks. Research bloods will be collected prior to treatment initiation and with radiologic assessments, and biobanked for future correlative analyses (including longitudinal ctDNA assessment). Archival tissue or a fresh biopsy will be collected during screening for all patients. Patients who achieve partial response will undergo on-treatment and post-progression biopsies for correlative analyses (including whole genome and transcriptome sequencing and multiplex immunohistochemistry). This study opened in August 2025 and is actively recruiting. Planned enrollment is 20 patients, with accrual expected to complete by June 2027. Clinical trial information: NCT07014137 .