WAILEA, Hawaii — The combination of durvalumab and tremelimumab appeared safe and demonstrated modest activity for heavily pretreated patients with a variety of sarcoma subtypes, according to single-center phase 2 study results presented at the Connective Tissue Oncology Society Annual Meeting.
Durvalumab (Imfinzi, AstraZeneca) and tremelimumab (MedImmune) showed especially promising activity among patients with alveolar soft part sarcoma, and that cohort continues to enroll patients.
“Anti-PD-1 therapy with pembrolizumab (Keytruda, Merck) has shown encouraging single-agent activity in undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma,” Neeta Somaiah, MD, assistant professor of sarcoma medical oncology at The University of Texas MD Anderson Cancer Center, said during her presentation. “The combination of anti-PD-1/PD-L1 with anti-CTLA-4 also has shown increased efficacy in melanoma and other cancers.”
Thus, Somaiah and colleagues sought to determine the efficacy of durvalumab, an anti-PD-1 agent, and tremelimumab, an anti-CTLA-4 agent, in multiple sarcoma subtypes and identify immune markers of response or resistance.
Researchers evaluated data from 46 patients aged at least 12 years with previously treated metastatic sarcoma. Cohorts of patients included those with liposarcoma (n = 6; mean age, 64.2 years), vascular sarcomas (n = 11; mean age, 53.9 years), undifferentiated pleomorphic sarcoma (n = 4; mean age, 56.4 years) , synovial sarcomas (n = 4; mean age, 32.8 years), osteosarcoma (n = 5; mean age, 45.8 years), alveolar soft part sarcoma (n = 6; mean age, 37.8 years) and others (n = 10; mean age, 43.2 years).
Patients received 1,500 mg durvalumab with 75 mg tremelimumab every 4 weeks for four cycles, followed by 1,500 mg durvalumab every 4 weeks.
PFS rate at 12 weeks served as the study’s primary endpoint. Using Bayesian modeling, researchers would close study arms if their PFS rate at 12 weeks was unlikely to exceed 40%, or unacceptable toxicity would exceed 30%.
Secondary endpoints included safety/tolerability, response and survival.
Partial response occurred in one patient each with undifferentiated pleomorphic sarcoma (25%) and angiosarcoma (20%), and three patients with alveolar soft part sarcoma (50%). The disease control rate for alveolar soft part sarcoma was 83%.
After a median follow-up of 3.7 months (range, 0.9-14.8), median OS was 14.5 months (95% CI, 4.7-not reached), and median PFS was 4.1 months (95% CI, 2.8-5.5).
All six patients with alveolar soft part sarcoma remained on the study at the time of the analysis, three of whom showed a decrease in tumor volume.
Seventeen grade 3 or worse treatment-related adverse events occurred in 10 patients (21.7%), including colitis, nausea, cardiac dysfunction, thyroiditis, pneumonitis, hepatitis, myositis, anemia and fatigue.
When researchers compared baseline and 6-week biopsies, they observed an increase in immune infiltrate CD3+ on treatment among two of four patients with liposarcoma, one patient with undifferentiated pleomorphic sarcoma, three of three patients with osteosarcoma, and two of three patients with alveolar soft part sarcoma.
This increase in immune infiltrate might be an indicator of response or disease stabilization, Somaiah said. – by Alexandra Todak
Somaiah N, et al. Abstract 010. Presented at: CTOS Annual Meeting; Nov. 8-11, 2017; Maui, Hawaii.
Disclosures: The authors report no relevant financial disclosures.