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A Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma
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DOI：10.1038/s41416-026-03574-z.png)
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Abstract
En 中文
Ontorpacept, a recombinant signal regulatory protein alpha (SIRPα)–blocking fusion protein, has antitumour activity by disrupting CD47–SIRPα signalling. This Phase 1/2 study examined ontorpacept with doxorubicin in patients with leiomyosarcoma. Eligible patients were ≥18 years with metastatic or locally advanced high-grade soft-tissue sarcomas (high-grade leiomyosarcoma in Phase 2). In Phase 1, patients received escalating doses of ontorpacept plus doxorubicin. Phase 2 dose expansion evaluated ontorpacept doses 0.2, 1.0, and 2.0 mg/kg plus doxorubicin. The primary endpoints were safety (Phase 1); and objective response rate (ORR) (Phase 1/2). Seventy-six patients were enrolled (Phase 1, n = 9; Phase 2, n = 67). No dose-limiting toxicities occurred in Phase 1. The most common treatment-related adverse events were neutrophil count decreased/neutropenia (grade ≥3 in 66% of patients). 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 2.0 mg/kg (ORR, 4.5%; 95% CI, 0.1–22.8) had confirmed partial responses. This first study of CD47 inhibition with chemotherapy in leiomyosarcomas shows manageable safety, supporting further investigation of ontorpacept dosing and schedule, in combination with doxorubicin and as monotherapy.
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