Sitravatinib Yields Meaningful Disease Control in Liposarcoma Subtypes

Treatment with sitravatinib (MGCD516) resulted in a positive progression-free rate (PFR) and meaningful disease control in a population of patients with advanced well-differentiated/dedifferentiated liposarcoma, according to data from a phase 2 study (NCT02978859).

"Sitravatinib was generally well tolerated and most adverse [effects; AEs] were low grade and consistent with the known [AE] profile of the drug," according to the authors of a phase 2 study.

Of the study’s total patient population (n = 29), 41% were alive and progression-free at 12 weeks, although there were no reported complete responses. A total of 38% of patients met the 12-week PFR end point. Additionally, the median progression-free survival (PFS) was 11.7 weeks (95% CI, 5.9-35.9), and the median overall survival (OS) was 31.7 weeks (95% CI, 18.1-90.1).

“Although purely [well-differentiated liposarcoma] exhibits a more indolent natural history than [dedifferentiated liposarcoma], these tumors still cause considerable morbidity and require systemic treatment when surgical options are exhausted,” the authors wrote. “For this reason, patients with progressive, unresectable [well-differentiated liposarcoma] were included on this study. Sitravatinib was generally well tolerated and most adverse [effects; AEs] were low grade and consistent with the known [AE] profile of the drug.”

The study included patients 18 years and older with histologically confirmed disease. Moreover, patients needed to undergo treatment with at least 1 systemic therapy in the neoadjuvant, adjuvant, or metastatic settings. Additional inclusion criteria included radiographic evidence of progression within 12 weeks of enrollment, an ECOG performance status of 0 or 1, and adequate organ function.

Investigators of the single-arm, multi-center clinical trial used a Simon 2 stage design and recruited patients via several institutions, including Columbia University Irving Medical Center; Siteman Cancer Center, Washington University in St. Louis; and Massachusetts General Hospital Cancer Center.

The primary end point was PFR, with key secondary end points including objective response, PFS, OS, and safety.

Those who enrolled on the study received 150 mg of oral sitravatinib in 21-day cycles. Following enrollment of 8 patients, the starting dose was decreased to 120 mg. Treatment continued until disease progression, unacceptable AEs, consent withdrawal, or intercurrent illness preventing further treatment.

Enrollment took place from March 2017 to August 2020. The median patient age was 62 years. Moreover, 55% of patients were male, and 76% were Caucasian. The majority of patients had dedifferentiated liposarcoma or mixed dedifferentiated/well-differentiated disease (93%), while fewer had well-differentiated disease only (7%).

Thirty-one percent of patients had received 3 or more prior lines of therapy, with commonly used agents including CDK4/6 inhibitors (41%), anthracycline- (41%) or gemcitabine-based (34%) chemotherapy, eribulin (25%), MDM2 inhibitors (17%), and immunotherapy (17%).

All patients had discontinued treatment as of the trial’s data cutoff of May 31, 2022—most commonly due to disease progression (83%), AEs (10%), and withdrawal of consent (7%).

Investigators reported that 50% of patients met the PFR end point at the 150 mg dose level vs 38% who received the 120 mg dose. A single patient achieved a partial response, although this was interrupted by concurrent COVID-19 infection. A total of 28% of patients experienced some degree of tumor regression while on treatment. Additionally, 5 patients had stable disease for over 30 weeks.

A total of 86% of patients experienced any-grade AEs. Common any-grade treatment-related AEs (TRAEs) included diarrhea (59%), hypertension (52%), fatigue (45%), hoarseness (41%), mucositis (31%), and nausea (31%). Additionally, 38% of patients had grade 3 TRAEs such as hypertension (21%), fatigue (7%), oral mucositis (3%), anemia (3%), and weight loss (3%). There was 1 event of grade 4 hypertension.

Reference

Ingham M, Lee S, Van BA, et al. A single-arm phase II trial of sitravatinib in advanced well-differentiated/dedifferentiated liposarcoma. Clin Can Res. 2023;29(6):1031-1039. doi:10.1158/1078-0432.CCR-22-3351