maplirpacept (TTI-622) / Pfizer - LARVOL DELTA

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

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=8 | Active, not recruiting | Sponsor: Pfizer | Recruiting ➔ Active, not recruiting

Enrollment closed • Metastases • Monotherapy • Hematological Disorders • Hematological Malignancies • Lymphoma • Multiple Myeloma • Non-Hodgkin’s Lymphoma • Oncology

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: Mar 2028 ➔ Nov 2027 | Trial primary completion date: May 2026 ➔ Dec 2025

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

Effects of Maplirpacept (PF-07901801),Tafasitamab, and Lenalidomide in People With Relapsed or Refractory Diffuse Large B-cell Lymphoma (clinicaltrials.gov) - P1/2 | N=70 | Recruiting | Sponsor: Pfizer | Phase classification: P2 ➔ P1/2

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

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=70 | Recruiting | Sponsor: Pfizer | Trial completion date: Jun 2028 ➔ Oct 2028 | Trial primary completion date: Jun 2026 ➔ Oct 2026

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

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=70 | Recruiting | Sponsor: Pfizer | Trial completion date: Feb 2029 ➔ Jun 2028 | Trial primary completion date: Feb 2027 ➔ Jun 2026

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

Heterogeneity of immune status in patient-derived malignant pleural effusion and ascites: Relationship to the ex-vivo efficacy of a HER2-targeted tri-specific antibody and a novel cytokine fusion protein. (ASCO 2024) - "IAMA-004 and IAMA-005 enhanced the killing of Her2 positive tumor cells by ~30% and ~40% respectively; Herceptin plus TTI-622 was not able to enhance the tumor cell killing. In combination with nivolumab, IAMA-004 was able to enhance the Granzyme B and IFN-γ secretion significantly without enhancing the tumor cell killing... Immune status from MPE or MA are heterogenous in both adaptive and innate immunity. Using combinations of innate immune targeting therapeutics and adaptive immune check point inhibitors may be able to correct the specific deficiency with precision and effectively treat these diseases."

Heterogeneity • Pleural effusion • Preclinical • Trispecific • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Ovarian Cancer • Respiratory Diseases • Solid Tumor • CD4 • CD8 • GZMB • HER-2 • IFNG

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 primary completion date: Feb 2026 ➔ May 2026

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

A phase I/II study of maplirpacept in combination with pegylated liposomal doxorubicin (PLD) in patients with platinum-resistant ovarian cancer (OC): Phase 1 results. (ASCO 2024) - P1/2 | "PLD 40mg/m2 conveyed poor efficacy (PFS 4 months; ORR 8%), as did bevacizumab + PLD (PFS 5 months; ORR 14%) (AURELIA), highlighting the need for new treatments for platinum-resistant OC. Despite immature anti-tumor activity, maplirpacept + PLD was tolerable at all dose levels, not reaching the MTD. The encouragingly tolerable dose of 48mg/kg thus represents the RP2D which could support further development for this population. Clinical trial information: NCT05261490."

Clinical • Combination therapy • P1/2 data • Oncology • Ovarian Cancer • Solid Tumor • CD47 • SIRPA

The CD47-blocking immune checkpoint inhibitor maplirpacept does not interfere with blood transfusion compatibility testing (BSH 2024) - "CD47 expression on RBCs has been shown to interfere with pre-transfusion laboratory testing in patients treated with the anti-CD47 mAb, Hu5F9-G4. In this study we demonstrate that interference with blood compatibility testing is dependent upon CD47-blocking agent type. Maplirpacept, unlike anti-CD47 mAbs, does not interfere with blood group serological testing, which may confer a significant clinical advantage by negating the need for approaches to prevent interference."

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