A Phase 1/2 study of ontorpacept (TTI-621) in combination with doxorubicin in patients with unresectable or metastatic high-grade leiomyosarcoma.
Sujana Movva, Victoria Allgood, Rashmi Chugh et al.
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In 30 seconds
This multicentre Phase 1/2 clinical trial evaluated ontorpacept, a CD47–SIRPα pathway inhibitor, with doxorubicin in adults with advanced high-grade soft-tissue sarcoma; Phase 2 enrolled patients with high-grade leiomyosarcoma. Among the Phase 2 dose groups, confirmed partial responses occurred in six patients receiving ontorpacept 0.2 mg/kg (ORR, 18.8%; 95% CI, 7.2-36.4) and one receiving 2.0 mg/kg (ORR, 4.5%; 95% CI, 0.1-22.8). No dose-limiting toxicities occurred in Phase 1. The authors described safety as manageable and supported further investigation.
Key findings
- In Phase 2, the ORR was 18.8% (95% CI, 7.2-36.4) with ontorpacept 0.2 mg/kg plus doxorubicin.
- With ontorpacept 2.0 mg/kg plus doxorubicin, the ORR was 4.5% (95% CI, 0.1-22.8).
- No dose-limiting toxicities occurred in Phase 1; grade ≥3 neutropenia or decreased neutrophil count affected 66% of patients.
Why it matters
The study provides early clinical evidence on combining CD47-pathway inhibition with doxorubicin in advanced leiomyosarcoma. The observed responses and reported safety profile may inform further evaluation of dose and schedule, while the differing response rates across dose groups underscore the need for additional evidence before drawing conclusions about efficacy.
What to keep in mind
This was an early-phase study with small dose groups, and the abstract reports no randomised comparator; response rates therefore do not establish comparative benefit.