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Background <p>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.</p> Methods <p>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).</p> Results <p>Seventy-six patients were enrolled (Phase 1, <i>n</i> = 9; Phase 2, <i>n</i> = 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.</p> Conclusions <p>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.</p>

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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

  • 期刊论文

  • 发表日期：

    2026年8月4日

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  • Sujana Movva,
  • Victoria Allgood,
  • Rashmi Chugh,
  • Lara E. Davis,
  • Howard H. Bailey,
  • Mohammed Milhem,
  • Varun Monga,
  • Steven Attia,
  • Ankit Mangla,
  • Ingmar Bruns,
  • Luke Kuttschreuter,
  • Dalila Bouyoucef-Cherchalli,
  • Caimiao Wei,
  • Gloria H. Y. Lin,
  • Hong Zhang,
  • Ilan Pomerance,
  • Mihaela Druta,
  • Sant Chawla

摘要

Background

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.

Methods

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).

Results

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.

Conclusions

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.