A phase II, multicenter trial of the combination of chidamide and toripalimab in patients with advanced soft tissue sarcoma: Efficacy updates.

Abstract

11560 Background: Chidamide is an oral subtype-selective histone deacetylase (HDAC) inhibitor which is effective on the patients with hematological tumors and could be hoped to enhance the efficacy of checkpoint blockade therapies and regulate the host immune response. Here, we report the updates of preliminary results of the combination of Chidamide and Toripalimab in soft tissue sarcoma (STS) patients. Methods: An open-label, single arm, multicenter, phase II study of Chidamide with Toripalimab in patients with advanced STS was conducted. Patients who were with failure or intolerance of standard systemic therpy, or no existed standard treatment, are eligible. Patients who had underwent HDAC inhibitors and immune checkpoint inhibitors treatment were excluded. All patients received Chidamide orally at 30mg twice weekly in combination with intravenous Toripalimab 240mg every 21 days until progression or unaccepte toxicity. The primary endpoint was RECIST1.1 objective response rate (ORR). The secondary endpoint included progression free survival (PFS), overall survival (OS), disease control rate (DCR) and safety. Results: At the data cut-off date (January, 2025),sixty-nine patients with advanced STS were enrolled. The median age of the patients was 47 years (range, 16 to 68) and the median prior lines of therapy were 2 (range, 0 to 5). The main subtypes included leiomyosarcoma (29%), well/dedifferentiated liposarcoma (36.2%), undifferentiated sarcoma(7.2%), myxoid/round cell liposarcoma (4.3%), and osteosarcoma (4.3%). Treatment was well tolerated with the most common adverse events mainly in grade 1-2, including anemia(55.1%), hypothyroidism(44.9%), leukopenia(33.3%), thrombocytopenia (30.4%), neutropenia(24.6%), nausea/vomit(24.6%), and fatigue (15.9%). Of the grade 3–4 adverse events, the most common were neutropenia(27.5%), thrombocytopenia (23.2%), leukopenia(14.5%), nausea/vomit(10.1%) and anemia(1.4%). Among 69 efficacy-evaluable patients, the ORR and DCR were 29% and 73.9%, respectively. The median time to an initial response was 5 months (95%CI 3-7), and the median PFS was 7.1 months（95%CI 4.0-10.2）, and the median OS was not reached. Conclusions: Chidamide with Toripalimab every 21 days was well tolerated and showed promising efficacy in patients with advanced STS. The exploratory biomarker study is ongoing. Clinical trial information: NCT04025931 .