The safety and efficacy of this agent(s), or use in this setting, has not been established or is subject to confirmation. For an agent(s) whose safety and efficacy has not been established or confirmed, future regulatory approval or commercial availability is not guaranteed.

Maplirpacept

Geo Regions

Maplirpacept

SIRPα-IgG4 Fusion Protein

Maplirpacept (TTI-622/PF-07901801) is an investigational compound. Its safety and efficacy have not been established.

Overview + Rationale

  • Maplirpacept (TTI-622/PF-07901801) is a fusion protein designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro-phagocytic signal via IgG4 Fc
  • Maplirpacept minimally binds to human red blood cells
RATIONALE FOR CANCER TYPE
  • CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body. It plays an integral role in various immune responses as well as autoimmunity, by sending a “don’t eat me” signal to prevent phagocytosis
  • CD47 is overexpressed in various hematological malignancies and its interaction with Signal Regulatory Protein (SIRP)α on phagocytic cells prevents phagocytosis of cancer cells
  • Additionally, it is expressed by different cell types in the tumor microenvironment and is required for establishing tumor metastasis. Overexpression of CD47 is thus often associated with poor clinical outcomes
  • CD47 blockade promotes both innate (macrophage phagocytosis) and adaptive immunity (T cell responses)
  • Tumor cells frequently overexpress CD47 and exploit this pathway to evade macrophage-mediated destruction

Mechanism of Action

Maplirpacept (TTI-622/PF-07901801) consists of the CD47-bindingdomain of human SIRPα and is linked to the Fc region of IgG4.

The IgG4 Fc delivers a moderate “eat” signal through FcγRs

Stage of Development

small icon for Hematologic Cancer
Advanced Hematological Malignancies including Lymphoma, Leukemia and Multiple Myeloma
Phase 1b/2 Monotherapy and Combination*
small icon for Hematologic Cancer
R/R Diffuse Large B-Cell Lymphoma (DLBCL)Transplant Ineligible
Phase 1b/2 Combinations

R/R=relapsed/refractory * Closed to Enrollment

REFERENCES: Eladl, E., J Hematol Oncol 13, 96 (2020); Thompson et al. Journal of Clinical Oncology 35, no. 15_supp https://medicalxpress.com/news/2017-02-potential-cancer-treatment-cancer-engulfing-cells.html Accessed Nov.22,2021; Patel et al. ASH 2020 Poster. 1191 https://ash.confex.com/ash/2020/webprogram/Paper136607.html. Accessed Nov. 23, 2021l Trillium R&D Day “Opening a NewChapter in Trillium’s Evolution,” April 2021; Trillium Therapeutics Annual Information Form for the Year Ending December 31, 2019; ClinicalTrials.gov. Accessed October 30, 2023. http://clinicaltrials.gov/