Multicenter phase 1-2 study of ontorpacept plus doxorubicin for unresectable or metastatic high-grade leiomyosarcoma

Ontopacept (TTI-621) is a recombinant signal regulatory protein alfa (SIRPα)-blocking fusion protein. It has antitumor activity by disrupting CD47-SIRPα signalling. A multicenter phase 1-2 study in the USA evaluated ontorpacept plus doxorubicin in adult patients with unresectable or metastatic (U/M) high-grade leiomyosarcoma (LMS). Eligible patients in phase 1 had soft-tissue sarcoma (n=9), while in phase 2 LMS patients were included (n=67). Patients received ontorpacept 0.2, 1.0, and 2.0 mg/kg plus doxorubicin. In phase 1, no dose-limiting toxicities occurred. The most common treatment-related adverse events were neutrophil count decreased/neutropenia (grade ≥3 in 66%). In phase 1, one patient receiving ontorpacept 2.0 mg/kg had a confirmed partial response. In phase 2, six patients receiving ontorpacept 0.2 mg/kg (ORR 18.8%; 95% CI 7.2-36.4) and one patient receiving ontorpacept 2.0 mg/kg (4.5%; 0.1-22.8) had confirmed partial responses. The authors conclude that in this first study of CD47 inhibition in combination with chemotherapy in LMS safety was manageable, supporting further investigation on ontorpacept dosing and schedule , in combination with doxorubicin and as monotherapy.