1941P - Preliminary efficacy and safety of SHR-2554 in advanced epithelioid sarcoma: A phase II trial

Background

Epithelioid sarcoma (ES) is a rare and aggressive subtype of soft-tissue sarcoma. The loss of INI1 expression which leads to oncogenic dependence on the transcriptional repressor EZH2 has been observed in over 90% of ES. There remains a need for effective and safe treatment options for patients (pts) with advanced ES. We investigated the efficacy and safety of SHR-2554, an oral selective EZH2 inhibitor, in pts with refractory ES.

Methods

Pts were eligible if they were aged 12 years or older with histologically confirmed advanced or metastatic ES. Other key inclusion criteria: the presence of measurable disease according to RECIST 1.1; an ECOG performance status of 0-1; progressive disease after at least one line of adriamycin containing chemotherapy; documented loss of SMARCB1 (INI1) alterations or the upregulated mRNA level of EZH2. Pts received SHR2554 (350 mg, bid, po) until disease progression or unacceptable toxicity. The primary endpoint was progression-free rate at 12 weeks. A Simon two-stage design was applied. Success at stage 1, which would enroll 9 pts, required ≥3 pts remaining progression-free at 12 weeks.

Results

Between Jul 2021 and Dec 2022, a total of 9 pts were enrolled and received SHR-2554. The median age was 44 years and 33.3% were males. 5 (55.6%) pts had received previous immunotherapy targeting PD-1/L1 and 4 (44.4%) pts had received previous antiangiogenesis therapy. The median line of previous treatment was 2 (range 1-4). Loss of INI1 was confirmed in 6 (66.7%) pts. 5 (55.6%) pts remained progression-free at 12 weeks, which allowing to move on to stage 2. Based on investigator assessments, one (11.1%) of 9 pts had a confirmed partial response at data cutoff. The median progression-free survival was 3.8 months (95% CI: 1.2–NA). Adverse events (AEs) were generally mild. The most common treatment-related AEs were anaemia (3, 33.3%). No serious treatment-related AEs were observed.

Conclusions

SHR-2554 showed promising efficacy and an acceptable safety profile in pts with refractory ES, warranting further investigation.

Clinical trial identification

ChiCTR2100046099.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Jiangsu Hengrui Pharmaceuticals Co., Ltd.

Disclosure

All authors have declared no conflicts of interest.