Phase I study of the CD47 blocker TTI-621 in patients with relapsed or refractory hematologic malignancies

Stephen M. Ansell, Michael B. Maris, Alexander M. Lesokhin, Robert W. Chen, Ian W. Flinn, Ahmed Sawas, Mark D. Minden, Diego Villa, Mary Elizabeth M. Percival, Anjali S. Advani, James M. Foran, Steven M. Horwitz, Matthew G. Mei, Jasmine Zain, Kerry J. Savage, Christiane Querfeld, Oleg E. Akilov, Lisa D.S. Johnson, Tina Catalano, Penka S. PetrovaRobert A. Uger, Eric L. Sievers, Anca Milea, Kathleen Roberge, Yaping Shou, Owen A. O'Connor

Research output: Contribution to journalArticlepeer-review


Purpose: TTI-621 (SIRPα-IgG1 Fc) is a novel checkpoint inhibitor that activates antitumor activity by blocking the CD47 "don't eat me"signal. This first-in-human phase I study (NCT02663518) evaluated the safety and activity of TTI-621 in relapsed/refractory (R/R) hematologic malignancies. Patients and Methods: Patients with R/R lymphoma received escalating weekly intravenous TTI-621 to determine the maximum tolerated dose (MTD). During expansion, patients with various malignancies received weekly single-agent TTI-621 at the MTD; TTI-621 was combined with rituximab in patients with B-cell non- Hodgkin lymphoma (B-NHL) or with nivolumab in patients with Hodgkin lymphoma. The primary endpoint was the incidence/ severity of adverse events (AEs). Secondary endpoint included overall response rate (ORR). Results: Overall, 164 patients received TTI-621: 18 in escalation and 146 in expansion (rituximab combination, n = 35 and nivolumab combination, n = 4). On the basis of transient grade 4 thrombocytopenia, the MTD was determined as 0.2 mg/kg; 0.1 mg/kg was evaluated in combination cohorts. AEs included infusion-related reactions, thrombocytopenia, chills, and fatigue. Thrombocytopenia (20%, grade ≥3) was reversible between doses and not associated with bleeding. Transient thrombocytopenia that determined the initial MTD may not have been dose limiting. The ORR for all patients was 13%. The ORR was 29% (2/7) for diffuse large B-cell lymphoma (DLBCL) and 25% (8/32) for T-cell NHL (T-NHL) with TTI-621 monotherapy and was 21% (5/24) for DLBCL with TTI-621 plus rituximab. Further dose optimization is ongoing. Conclusions: TTI-621 was well-tolerated and demonstrated activity as monotherapy in patients with R/R B-NHL and T-NHL and combined with rituximab in patients with R/R B-NHL.

Original languageEnglish (US)
Pages (from-to)2190-2199
Number of pages10
JournalClinical Cancer Research
Issue number8
StatePublished - Apr 2021

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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