Phase II Study of Eribulin plus Pembrolizumab in Metastatic Soft-tissue Sarcomas: Clinical Outcomes and Biological Correlates

Abstract

Purpose: Eribulin modulates the tumor-immune microenvironment via cGAS-STING signaling in preclinical models. This non-randomized phase II trial evaluated the combination of eribulin and pembrolizumab in patients with soft tissue sarcomas (STS). Patients and Methods: Patients enrolled in one of three cohorts: leiomyosarcoma (LMS), liposarcomas (LPS), or other STS that may benefit from PD-1 inhibitors, including undifferentiated pleomorphic sarcoma (UPS). Eribulin was administered at 1.4 mg/m2 IV (days 1 and 8) with fixed-dose pembrolizumab 200 mg IV (day 1) of each 21-day cycle, until progression, unacceptable toxicity, or completion of 2 years of treatment. The primary endpoint was the 12-week progression-free survival rate (PFS-12) in each cohort. Secondary endpoints included the objective response rate (ORR), median PFS, safety profile, and overall survival (OS). Pre- and on-treatment blood specimens were evaluated in patients who achieved durable disease control (DDC) or progression within 12 weeks (early progression [EP]). Multiplexed immunofluorescence was performed on archival LPS samples from patients with DDC or EP. Results: Fifty-seven patients enrolled (LMS, n=19; LPS, n=20; UPS/other, n=18). The PFS-12 was 36.8% (90% confidence interval [CI] 22.5-60.4%) for LMS, 69.6% (54.5-89.0%) for LPS, and 52.6% (36.8-75.3%) for UPS/other cohorts. All 3 patients in the UPS/other cohort with angiosarcoma achieved RECIST responses. Toxicity was manageable. Higher interferon (IFN) alpha and IL-4 serum levels were associated with clinical benefit. Immune aggregates expressing PD-1 and PD-L1 were observed in a patient that completed 2 years of treatment. Conclusions: The combination of eribulin and pembrolizumab demonstrated promising activity in LPS and angiosarcoma.