Maplirpacept
| Clinical data | |
|---|---|
| Synonyms | PF-07901801, TTI-622 |
| Identifiers | |
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| E number | {{#property:P628}} |
| ECHA InfoCard | {{#property:P2566}} |
| Chemical and physical data | |
| Formula | C3436H5316N912O1060S24 |
| Molar mass | 77131.09 g·mol−1 |
Maplirpacept (development names PF-07901801, TTI-622) is an investigational fusion protein being developed by Pfizer as an immune checkpoint inhibitor for the treatment of various hematologic malignancies.[1][2] The compound was originally developed by Trillium Therapeutics before being acquired by Pfizer in 2021.[3]
Mechanism of action
Maplirpacept is a recombinant fusion protein consisting of the CD47-binding domain of human signal regulatory protein alpha (SIRPα) linked to the IgG4 Fc region of human immunoglobulin G4.[2] The drug acts as an innate immune checkpoint inhibitor that prevents CD47-SIRPα binding, engages activating Fcγ receptors on macrophages, and promotes phagocytosis of malignant cells.[4] It is administered intravenously.
CD47, or integrin-associated protein, is a cell surface ligand expressed in low levels by nearly all cells of the body and plays an integral role in various immune responses by sending a "don't eat me" signal to prevent phagocytosis.[1] CD47 is highly expressed on cancer cells and triggers an anti-phagocytic "don't eat me" signal when bound by the inhibitory signal regulatory protein α (SIRPα) expressed on macrophages.[5]
Maplirpacept functions as a soluble decoy receptor, preventing CD47 from delivering its antiphagocytic signal.[6]
Red blood cell binding characteristics
Maplirpacept is a CD47 blocking fusion protein designed to limit binding to red blood cells (RBCs).[7] This design feature is important because while CD47 blockade can mitigate tumor growth, many CD47 blockers also bind to red blood cells.[5]
Clinical development
Phase I/II trials
Maplirpacept is currently being evaluated in multiple clinical trials for various hematologic malignancies:
- NCT05896163: A multicenter, open-label, Phase 1b/2 study to evaluate the safety, tolerability and potential clinical benefits of maplirpacept in combination with fixed doses of glofitamab after a single dose of obinutuzumab in participants with relapsed/refractory diffuse large B-cell lymphoma.[8]
- NCT05567887: A study evaluating maplirpacept in Japanese patients with hematologic malignancies.[6]
- NCT05896774: Additional clinical trial for maplirpacept evaluation.[9]
- NCT03530683: A Phase 1a/1b clinical trial evaluating maplirpacept alone and in combination with other medicines for advanced hematological malignancies including lymphoma, leukemia and multiple myeloma that was terminated.[10]
Development challenges
In 2025, Pfizer ended a mid-stage trial for the CD47 blood cancer drug, citing recruitment problems. According to an update to a federal clinical trials database, the study was dropped because of the "inability to recruit the planned number of subjects." Only six had been enrolled into the trial since it began in August 2023.[11][12]
Multiple myeloma development
Maplirpacept is under clinical development by Pfizer and currently in Phase II for Relapsed Multiple Myeloma. According to GlobalData, Phase II drugs for Relapsed Multiple Myeloma have a 37% phase transition success rate (PTSR) indication benchmark for progressing into Phase III.[13]
Laboratory considerations
Maplirpacept does not interfere with blood transfusion compatibility testing, which is an important clinical consideration for patients receiving treatment.[14]
Side effects and safety profile
Based on data from the ongoing first-in-human dose escalation study, the most frequent treatment-related adverse events include thrombocytopenia (affecting 21% of patients), neutropenia (12%), and anemia and fatigue (9% each).[15]
Related adverse events of Grade 3 or higher intensity include thrombocytopenia (5% of patients; 1 each Grade 3 and 4), neutropenia (9%; all Grade 3), and anemia. The safety profile reflects the mechanism of action involving immune system modulation and potential effects on hematopoiesis (blood cell production).
As an investigational compound, the safety and efficacy of maplirpacept has not been established and comprehensive safety data are still being collected through ongoing clinical trials.[16]
Regulatory status
As of September 2025, maplirpacept remains an investigational compound with safety and efficacy not yet established by regulatory authorities.[1] The drug is being developed under various clinical trial protocols registered with regulatory agencies including the U.S. Food and Drug Administration (FDA) and international equivalents.
See also
- CD47
- Immune checkpoint inhibitor
- Fusion protein
- Hematologic malignancy
- Diffuse large B-cell lymphoma
- Multiple myeloma
References
- ↑ 1.0 1.1 1.2 "Maplirpacept (TTI-622 | PF-07901801)". Pfizer Oncology Development. Retrieved 2025-09-12.
- ↑ 2.0 2.1 "Maplirpacept: Uses, Interactions, Mechanism of Action". DrugBank Online. Retrieved 2025-09-12.
- ↑ "Pfizer Bets $2.26 Billion on Trillium's Checkpoint Inhibitors". BioSpace. 2021-08-23. Retrieved 2025-09-12.
- ↑ Multiple authors (2023). "The CD47-Blocking Immune Checkpoint Inhibitor Maplirpacept Does Not Interfere with Blood Transfusion Compatibility Testing". Blood. 142 (Supplement 1): 4037. doi:10.1182/blood-2023-174949.
- ↑ 5.0 5.1 Krishnamoorthy M, Seelige R, Christopher R, Chau N, Nielsen VN, Lisa DS, Linderoth E, Jean CY, Christopher P, Abayasiriwardana K, Lees C, Wong M, Megan M, Robert A, Gloria HY (2025). "Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy". Frontiers in Immunology. 16. doi:10.3389/fimmu.2025.1518787. PMC 11897230 Check
|pmc=value (help). PMID 40078999 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ 6.0 6.1 "A Study to Learn About the Study Medicine (Called Maplirpacept (PF-07901801)) in Japanese With Hematologic Malignancies". ClinicalTrials.gov. 5 November 2024. Retrieved 2025-09-12.
- ↑ Krishnamoorthy M, Seelige R, Brown CR, Chau N, Nielsen Viller N, Johnson LD, Linderoth E, Wang JC, Dillon CP, Abayasiriwardana K, Lees C, Wong M, Kaneda MM, Uger RA, Lin GH (2025). "Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy". Frontiers in Immunology. 16. doi:10.3389/fimmu.2025.1518787. PMC 11897230 Check
|pmc=value (help). PMID 40078999 Check|pmid=value (help). Unknown parameter|article-number=ignored (help) - ↑ "A Study to Learn About the Effects of Two Study Medicines (Maplirpacept [PF-07901801] And Glofitamab) When Given Together In People With Relapsed Or Refractory Diffuse Large B Cell Lymphoma". ClinicalTrials.gov. 24 June 2025. Retrieved 2025-09-12.
- ↑ Pfizer (2024-11-18). An Open-Label, Phase 1 Study Evaluating the Pharmacokinetics, Safety and Anti-Tumor Activity of PF-07901801 (TTI-622) Monotherapy in Chinese Participants With Advanced Hematologic Malignancies (Report). clinicaltrials.gov.
- ↑ Pfizer (2024-08-29). A Phase 1a/1b Dose-Escalation and Expansion Trial of TTI-622 in Patients With Advanced Hematologic Malignancies, Including Lymphoma, Leukemia, and Multiple Myeloma (Report). clinicaltrials.gov.
- ↑ "Pfizer Ends Mid-Stage Trial for CD47 Blood Cancer Drug, Citing Recruitment Problems". BioSpace. July 1, 2025. Retrieved 2025-09-12.
- ↑ Pfizer (2025-09-03). A PHASE 1b/2 STUDY OF PF-07901801, A CD47 BLOCKING AGENT, WITH TAFASITAMAB AND LENALIDOMIDE FOR PARTICIPANTS WITH RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA NOT ELIGIBLE FOR STEM CELL TRANSPLANTATION (Report). clinicaltrials.gov.
- ↑ "Maplirpacept by Pfizer for Relapsed Multiple Myeloma: Likelihood of Approval". Pharmaceutical Technology. April 19, 2024. Retrieved 2025-09-12.
- ↑ Krishnamoorthy M, Viller NN, Wong M, Dodge K, Pang X, Uger RA, Lin GH, Kaneda MM (2023). "The CD47-Blocking Immune Checkpoint Inhibitor Maplirpacept Does Not Interfere with Blood Transfusion Compatibility Testing". Blood. 142: 4037. doi:10.1182/blood-2023-174949. Retrieved 2025-09-12.
- ↑ Patel K, Zonder JA, Sano D, Maris M, Lesokhin A, von Keudell G, Lai C, Ramchandren R, Catalano T, Lin GH, Uger B, Petrova PS, Molloy N, Bruns I, Iyer SP (2021-11-05). "CD47-Blocker TTI-622 Shows Single-Agent Activity in Patients with Advanced Relapsed or Refractory Lymphoma: Update from the Ongoing First-in-Human Dose Escalation Study". Blood. 138 (Supplement 1): 3560. doi:10.1182/blood-2021-153683. ISSN 0006-4971. Archived from the original on 2025-06-24.
- ↑ "Maplirpacept Safety Information". Pfizer Oncology Development. Retrieved 2025-09-12.
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