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

Clin Cancer Res. 2024 Apr 1;30(7):1281-1292. doi: 10.1158/1078-0432.CCR-23-2250.


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 i.v. (days 1 and 8) with fixed-dose pembrolizumab 200 mg i.v. (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, median PFS, safety profile, and overall survival (OS). Pretreatment 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: 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 IFNα and IL4 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.

Publication types

  • Clinical Trial, Phase II

MeSH terms

  • Antibodies, Monoclonal, Humanized*
  • Furans*
  • Hemangiosarcoma*
  • Humans
  • Ketones*
  • Leiomyosarcoma*
  • Lipopolysaccharides / therapeutic use
  • Liposarcoma* / drug therapy
  • Polyether Polyketides*
  • Sarcoma* / pathology
  • Treatment Outcome
  • Tumor Microenvironment


  • eribulin
  • pembrolizumab
  • Lipopolysaccharides
  • Polyether Polyketides
  • Furans
  • Ketones
  • Antibodies, Monoclonal, Humanized