A single-arm phase 2 trial of Sitravatinib in advanced well-differentiated/dedifferentiated liposarcoma


 Purpose: To evaluate Sitravatinib, an inhibitor of multiple receptor tyrosine kinases (RTKs), for the treatment of well-differentiated/dedifferentiated liposarcoma (WD/DD LPS). Experimental Design: This multi-center, open-label, phase 2 trial enrolled patients with advanced WD/DD LPS who had received at least one prior systemic regimen and had progression within 12 weeks of enrollment. Patients received Sitravatinib 150 mg (later amended to 120 mg) orally daily. A Simon 2-stage design was used to evaluate for an improvement in the primary endpoint, progression-free rate at 12 weeks (PFR12), from 20% to 40%. Secondary endpoints included antitumor activity and safety. A subset of patients underwent paired biopsies analyzed using reverse phase protein array. Results: Twenty-nine patients enrolled. Median age was 62 years and 31% had received 3 or more prior lines. Most patients (93%) had DDLPS or mixed WD/DD LPS. Overall, 12 of 29 patients (41%) were alive and progression-free at 12 weeks and the study met the primary endpoint. There were no confirmed responses. Median PFS was 11.7 weeks (95% CI: 5.9 – 35.9) and median OS was 31.7 weeks (95% CI: 18.1 – 90.1). The most common treatment-related adverse events were diarrhea (59%), hypertension (52%), hoarseness (41%), mucositis (31%) and nausea (31%). Baseline expression of phospho-RTKs was not significantly different between patients with and without clinical benefit from Sitravatinib but the number of samples was small. Conclusions: Sitravatinib provided a progression-free rate at 12 weeks of 41% and meaningful disease control in a subset of patients with advanced, progressive WD/DD LPS.