maplirpacept (TTI-622) / Pfizer - LARVOL DELTA

Safety and pharmacokinetics of maplirpacept in Chinese patients with relapsed or refractory non-Hodgkin lymphoma (ESMO Asia 2025) - P1 | "Maplirpacept was well-tolerated in Chinese patients with R/R NHL with no new safety signals identified. Overall PK and safety profile was similar to that observed in Western countries."

Clinical • PK/PD data • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • SIRPA

A Multicenter, Open-Label, Phase 1b/2 Study to Evaluate the Effects of Maplirpacept in Combination with Glofitamab in People with Relapsed or Refractory Diffuse Large B Cell Lymphoma (ASH 2023) - P1, P1/2 | "Background Maplirpacept (PF-07901801) is an anti-CD47 fusion protein constructed to enhance phagocytosis and antitumor activity via inhibition of CD47-mediated signaling. All patients should have adequate bone marrow, hepatic, and renal function (eGFR ≥45 mL/min) and ECOG performance status ≤2. Exclusion criteria include prior treatment with an anti-CD47 agent, prior anti-CD20xCD3 containing regimen, refractoriness to an obinutuzumab monotherapy containing regimen, prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment, high grade B-cell lymphoma with BCL2 and Myc rearrangement, active bacterial, viral, fungal, mycobacterial, parasitic, or other infection."

Clinical • Combination therapy • P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Indolent Lymphoma • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Lymphoplasmacytic Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • T Cell Non-Hodgkin Lymphoma • Waldenstrom Macroglobulinemia • BCL2

A Multicenter, Open-Label, Phase 1b/2 Study to Evaluate the Effects of Maplirpacept in Combination with Tafasitamab and Lenalidomide in People with Relapsed or Refractory Diffuse Large B-Cell Lymphoma (ASH 2023) - P1, P1/2 | "Participants must provide a baseline tumor tissue sample (fresh or archival), for biomarker analysis. Exclusion criteria include previous treatment with anti-CD47, anti-CD19 (other than CAR-T) or immunomodulatory agents, prior allogeneic stem cell transplantation or autologous stem cell transplantation within 12 weeks prior to enrolment, and participants with active, uncontrolled viral, bacterial or fungal infections."

Clinical • Combination therapy • IO biomarker • P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Epstein-Barr Virus Infections • Follicular Lymphoma • Hematological Malignancies • Indolent Lymphoma • Infectious Disease • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Histiocyte Rich Large B Cell Lymphoma

The CD47-Blocking Immune Checkpoint Inhibitor Maplirpacept Does Not Interfere with Blood Transfusion Compatibility Testing (ASH 2023) - "CD47 expression on RBCs was shown to interfere with pre-transfusion laboratory testing in patients treated with the anti-CD47 mAb, Hu5F9-G4 (Velliquette et al. Here we demonstrate that interference with blood compatibility testing is dependent upon the type of CD47-blocking agent. Decoy receptors such as Maplirpacept, unlike anti-CD47 mAb, do not interfere with blood group serologic testing, which may confer a significant clinical advantage by negating the need for additional approaches to prevent interference."

Checkpoint inhibition • IO biomarker • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Lymphoma • Multiple Myeloma • Oncology • Ovarian Cancer • Solid Tumor • CD47 • SIRPA

A Study of TTI-622 in Combination With Daratumumab Hyaluronidase-fihj in People With Multiple Myeloma (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Memorial Sloan Kettering Cancer Center | Trial completion date: Oct 2025 ➔ Oct 2026 | Trial primary completion date: Oct 2025 ➔ Oct 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

HCB101: a novel potent ligand-trap Fc-fusion protein targeting the CD47-SIRPα pathway with high safety and preclinical efficacy for hematological and solid tumors. (PubMed, J Hematol Oncol) - "HCB101 demonstrates high-affinity binding to CD47, robustly promotes macrophage-mediated phagocytosis of tumor cells without affecting red blood cells and exhibits unique advantages over current CD47-targeting agents, including Hu5F9-G4, TTI-622, and ALX148. Additionally, HCB101 treatment increased the M1/M2 macrophage ratio in the tumor microenvironment, suggesting repolarization of tumor-associated macrophages (TAMs) toward a pro-inflammatory phenotype. No dose-limiting toxicities or hematologic adverse effects were observed in murine or non-human primate studies."

IO biomarker • Journal • Preclinical • Hematological Disorders • Oncology • Solid Tumor • CD47 • SIRPA

C4971006: 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) - P1/2 | N=24 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=70 ➔ 24 | Trial completion date: Sep 2028 ➔ Mar 2026 | Trial primary completion date: Sep 2026 ➔ Mar 2026

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

TTI-622 in Combination With Pembrolizumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=10 | Active, not recruiting | Sponsor: Mayo Clinic | Recruiting ➔ Active, not recruiting | N=41 ➔ 10 | Trial completion date: Nov 2027 ➔ Jul 2027 | Trial primary completion date: Nov 2026 ➔ Jul 2027

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • B Cell Lymphoma • B Cell Non-Hodgkin Lymphoma • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Large B Cell Lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Primary Cutaneous Diffuse Large B-Cell Lymphoma, Leg Type • Primary Mediastinal Large B-Cell Lymphoma • T Cell Histiocyte Rich Large B Cell Lymphoma • ALK • BCL2 • BCL6 • IRF4 • PD-L1

Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=6 | Terminated | Sponsor: Pfizer | Phase classification: P2 ➔ P1/2

Phase classification • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

Pfizer Ends Mid-Stage Trial for CD47 Blood Cancer Drug (PharmiWeb) - "Pfizer has discontinued its Phase 1b/2 trial of maplirpacept (PF-07901801), a CD47-blocking agent, in combination with tafasitamab and lenalidomide for relapsed or refractory diffuse large B-cell lymphoma (DLBCL) patients ineligible for stem cell transplantation. The trial, which began in August 2023, enrolled only six participants before being terminated due to recruitment challenges. Pfizer stated that the decision was not related to safety or efficacy concerns....The discontinuation adds to the challenges faced by CD47-targeting therapies."

Trial termination • Diffuse Large B Cell Lymphoma

Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P2 | N=6 | Terminated | Sponsor: Pfizer | Phase classification: P1/2 ➔ P2 | Active, not recruiting ➔ Terminated; The trial terminated due to the inability to recruit the planned number of subjects. The decision was not based on any safety and/or efficacy concerns

Phase classification • Trial termination • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

PHASE 1b/2 STUDY OF MAPLIRPACEPT (PF-07901801), TAFASITAMAB, AND LENALIDOMIDE IN TRANSPLANT-INELIGIBLE RELAPSED/REFRACTORY DIFFUSE LARGE B CELL LYMPHOMA PARTICIPANTS (ICML 2025) - P1/2 | "Addition of maplirpacept to tafasitamab and lenalidomide showed clinical activity and tolerable safety profile in pts with R/R DLBCL. Although this trial was discontinued due to enrollment challenges, further development of maplirpacept for R/R DLBCL continues in NCT05896163. A genAI tool (Feb25; Pfizer; GPT-4o) developed draft 1; authors assume content responsibility."

P1/2 data • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • SIRPA

Maplirpacept: a CD47 decoy receptor with minimal red blood cell binding and robust anti-tumor efficacy. (PubMed, Front Immunol) - "Moreover, phagocytosis of neoplastic cells can be enhanced when maplirpacept is combined with other therapeutic agents, including antibodies or chemotherapeutic agents. These preclinical results establish maplirpacept as an effective CD47 blocker that mitigates the potential for anemia in patients."

Journal • Hematological Disorders • Hematological Malignancies • Oncology • CD47 • SIRPA

MagnetisMM-20: A Clinical Trial of Four Medicines (Elranatamab Plus Carfilzomib and Dexamethasone or Maplirpacept) in People With Relapsed Refractory Multiple Myeloma (clinicaltrials.gov) - P1 | N=90 | Recruiting | Sponsor: Pfizer | Trial completion date: Nov 2027 ➔ Feb 2028 | Trial primary completion date: Dec 2025 ➔ Apr 2026

Trial completion date • Trial primary completion date • Hematological Malignancies • Multiple Myeloma • Oncology

A Study to Learn About the Study Medicine (Maplirpacept) in People With Advanced Non-Hodgkin Lymphoma or Multiple Myeloma in China (clinicaltrials.gov) - P1 | N=10 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed | Trial completion date: May 2025 ➔ Nov 2024

Metastases • Monotherapy • Trial completion • Trial completion date • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

Study of Maplirpacept (PF-07901801) in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P1/2 | N=10 | Terminated | Sponsor: Pfizer | Phase classification: P2 ➔ P1/2

Combination therapy • Phase classification • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

A Study to Learn About the Study Medicine (Called Maplirpacept (PF-07901801)) in Japanese With Hematologic Malignancies (clinicaltrials.gov) - P1 | N=7 | Completed | Sponsor: Pfizer | Active, not recruiting ➔ Completed

Trial completion • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Oncology

Study of Maplirpacept (PF-07901801) in Combination With PLD in Patients With Platinum-Resistant Ovarian Cancer (clinicaltrials.gov) - P2 | N=10 | Terminated | Sponsor: Pfizer | Phase classification: P1/2 ➔ P2

Combination therapy • Phase classification • Fallopian Tube Cancer • Oncology • Ovarian Cancer • Peritoneal Cancer • Solid Tumor

Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: Pfizer | Trial primary completion date: May 2025 ➔ Aug 2024

Trial primary completion date • B Cell Lymphoma • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation

A Study to Learn About the Study Medicine (Called Maplirpacept (PF-07901801)) in Japanese With Hematologic Malignancies (clinicaltrials.gov) - P1 | N=7 | Active, not recruiting | Sponsor: Pfizer | Trial completion date: Jul 2024 ➔ Oct 2024 | Trial primary completion date: Jul 2024 ➔ Oct 2024

Trial completion date • Trial primary completion date • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Lymphoma • Multiple Myeloma • Oncology

The CD47-blocking immune checkpoint inhibitor maplirpacept does not interfere with blood transfusion compatibility tests (DGHO 2024) - "Interference with RBC panel testing has important consequences in transfusion medicine as the presence of irregular antibodies can complicate the selection of suitable RBC units for treated patients. We demonstrated that interference with blood compatibility testing is dependent upon CD47-blocking agent type. Maplirpacept, unlike anti-CD47 mAbs, does not interfere with blood group serologic testing, which may confer a significant clinical advantage by negating the need for approaches to prevent interference."

Checkpoint inhibition • IO biomarker • Oncology • CD47 • SIRPA

Cancelled: Mitigating Anti-CD47 Interference Using Anti-human Globulin Clone Specific Reagent (AABB 2024) - "Gamma-clone AHG reagent, which does not detect IgG4, is shown to be effective in mitigating interference during pre-transfusion testing for Hu5F9-G4 or TTI-622 patients. Anti-CD47 mAbs of the IgG1 subclass, such as ALX-148, consistently cause interference regardless of the AHG reagent used. The implementation of clone specific AHG in pre-transfusion testing based on the patient treatment would support the patients' transfusion needs."

IO biomarker • Oncology • CD47

TTI-622 in Combination with Pembrolizumab for the Treatment of Relapsed or Refractory Diffuse Large B-Cell Lymphoma (clinicaltrials.gov) - P2 | N=41 | Recruiting | Sponsor: Mayo Clinic | N=62 ➔ 41

Combination therapy • Enrollment change • Diffuse Large B Cell Lymphoma • Follicular Lymphoma • Hematological Malignancies • High-grade B-cell lymphoma • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • T Cell Histiocyte Rich Large B Cell Lymphoma • ALK • BCL2 • BCL6 • IRF4 • PD-L1

TTI-622-01: A Clinical Trial to Learn About the Study Medicine Called Maplirpacept (PF-07901801), Alone and When Used in Combination With Other Medicines to Treat Participants With Advanced Hematological Malignancies, Including Lymphoma, Leukemia and Multiple Myeloma (clinicaltrials.gov) - P1 | N=189 | Terminated | Sponsor: Pfizer | Active, not recruiting ➔ Terminated; A business decision was made by Pfizer to terminate the study. Termination was not due to any safety concerns, requests from regulatory authorities, changes to the benefit/risk profile or any new concerns regarding the investigational product.

Combination therapy • Metastases • Trial termination • Acute Myelogenous Leukemia • Diffuse Large B Cell Lymphoma • Hematological Disorders • Hematological Malignancies • Hodgkin Lymphoma • Leukemia • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology • TP53

Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=4 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting | N=70 ➔ 4 | Trial completion date: Feb 2029 ➔ May 2025 | Trial primary completion date: Feb 2027 ➔ May 2025

Enrollment change • Enrollment closed • Trial completion date • Trial primary completion date • Bone Marrow Transplantation • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • Transplantation