magrolimab (ONO-7913) / Ono Pharmaceutical, Gilead - LARVOL DELTA

Magrolimab plus azacitidine vs physician's choice for untreated TP53-mutated acute myeloid leukemia: the ENHANCE-2 study. (PubMed, Blood) - P3 | "Patients determined inappropriate for intensive therapy were randomized to receive Magro/Aza or venetoclax plus azacitidine (Ven/Aza); those appropriate for intensive therapy were randomized to receive Magro/Aza or 7+3 induction chemotherapy. ENHANCE-2 did not meet its primary endpoint of OS in TP53-mutated AML but provides important data informing future studies in this challenging population. This trial was registered at www.clinicaltrials.gov as #NCT04778397."

Journal • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • TP53

Azacitidine, Venetoclax and Magrolimab in Newly Diagnosed and Relapsed Refractory Acute Myeloid Leukemia: Phase 1b/2 Study and Correlative Analysis. (PubMed, Clin Cancer Res) - "The triplet regimen was safe but did not lead to promising survival outcomes."

Journal • P1/2 data • Acute Myelogenous Leukemia • Hematological Malignancies • Infectious Disease • Leukemia • Oncology • CD47 • IFNG • TNFA • TP53

Phase II study of magrolimab combination therapies in patients with head and neck squamous-cell carcinoma. (PubMed, ESMO Open) - "There was no benefit observed with magrolimab treatment. The study closed prematurely, limiting interpretation."

Journal • P2 data • Head and Neck Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

EMP2 is a potential immunotherapeutic target to modulate macrophage-induced phagocytosis in glioblastoma (AACR 2026) - "Although, CD47 blockade enhances phagocytosis in preclinical models, clinical trials of anti-CD47 therapies such as magrolimab were halted due to increased mortality and limited efficacy in acute myeloid leukemia patients, highlighting the need for alternative phagocytosis-inducing therapies...Ongoing studies aim to validate that EMP2 knockout enhances macrophage phagocytosis in syngeneic murine GBM model. Collectively, our findings highlight EMP2 as a novel regulator of macrophage-mediated tumor clearance and a promising therapeutic target for macrophage-based immunotherapy in GBM."

IO biomarker • Acute Myelogenous Leukemia • Brain Cancer • Glioblastoma • Glioma • Hematological Malignancies • Leukemia • Oncology • Solid Tumor • KRAS • SIRPA

CD47 blockade induces necroptosis and complements the effects of BCL-2 inhibition in hematologic malignancies (AACR 2026) - "This cell death mechanism has yet been well-characterized, thus warranting investigation to comprehensively unravel the mechanism of CD47 blockade and to facilitate the identification of optimal drug partners for combination therapy. Anti-CD47 monoclonal antibodies (mAb), SRF231, magrolimab, B6H12, were evaluated for cell death mechanisms such as apoptosis, autophagy or necroptosis. Our study unravels a novel cell death mechanism of CD47 blockade through necroptosis, thereby permitting the inclusion of venetoclax-induced apoptosis, a complementary combination worthy of further study against BCL-2 dependent hematologic malignancies in the clinic."

Acute Myelogenous Leukemia • B Cell Lymphoma • Diffuse Large B Cell Lymphoma • Hematological Malignancies • Leukemia • Lymphoma • Non-Hodgkin’s Lymphoma • Oncology • ANXA5

PHST001, a humanized anti-CD24 hIgG4 antibody, is effective against metastatic tumors and retains its anti-tumor activity in the presence of competing IgG (AACR 2026) - "In vivo, PHST001 shows significantly greater efficacy against solid tumors than the anti-CD47 antibody Magrolimab...When combined with a companion agent, such as the anti-Her2 ADC trastuzumab deruxtecan, the Fc-inert version of PHST001 dramatically increased phagocytosis, demonstrating the contribution of CD24 blockade to PHST001 efficacy in absence of direct Fc receptor engagement... PHST001 prevents metastatic spread and demonstrates anti-tumor activity against established metastases. In vitro, peripheral blood cells expressing CD24 are protected from PHST001-mediated phagocytosis due to competition for Fc receptors by high levels of endogenous IgG, predicting protection in treated patients. PHST001 retains anti-tumor effects in vivo despite polyclonal IgG presence, indicating that competition for Fc receptors by endogenous IgG is not a barrier for efficacy in the tumor microenvironment."

Metastases • Breast Cancer • HER2 Breast Cancer • HER2 Positive Breast Cancer • Oncology • Solid Tumor • CD24

A novel humanized mouse model for preclinical assessment of anti-CD47 and anti-SIRPΑtherapeutics (AACR 2026) - "This model was used to evaluate the anti-tumor efficacy of the anti-hCD47 antibody Magrolimab (5F9) using a CT26-hCD47 colorectal tumor model—established by engrafting CT26 overexpressing human CD47 into BALB/c-hCD47/hSIRPΑ mice... The BALB/c-hCD47/hSIRPΑ mouse model serves as a clinically relevant tool for evaluating therapeutics targeting the CD47-SIRPΑ pathway within an immuocompetent model. Notably, it addresses key limitations of traditional immunocompromised murine models while providing critical insights into the mechanisms underlying CD47 pathway-mediated tumor clearance, toxicity management, and immune activation."

IO biomarker • Preclinical • Breast Cancer • Colorectal Cancer • Oncology • Solid Tumor • Triple Negative Breast Cancer • CD47 • CLDN18 • SIRPA

Tumor-activated PrimeBody biologics platform enables more potent CD47 targeting and superior therapeutic index in preclinical models (AACR 2026) - "Consequently, VOR-101 achieves >700-fold tumor-to-serum selectivity, a major improvement over the <25-fold selectivity observed with benchmark linkers currently in clinical development.In a translational hCD47/hSIRPα mouse model, magrolimab induced 50-60% depletion of red blood cells (RBCs) and exhibited poor systemic exposure (~10 nM)...In xenograft models, VOR-101 induced durable complete responses that persisted well beyond the dosing period.Together, these findings demonstrate that VOR-101 (a tumor-activated, Fc-enhanced, high-affinity CD47 blocker) significantly improves the therapeutic index in preclinical models compared to clinical comparators. VOR-101 is advancing through IND-enabling studies with potential to exhibit single-agent activity in solid tumors."

Preclinical • Oncology • Solid Tumor • CD47 • SIRPA

Exercise-mobilized lymphocytes enhance antibody-based immunotherapy in multiple myeloma through CD16+ NK cell-mediated cytotoxicity. (PubMed, J Transl Med) - No abstract available

Journal • Hematological Malignancies • Multiple Myeloma • Oncology

Νοvel Therapies in High-Risk Myelodysplastic Syndromes. (PubMed, Eur J Haematol) - "Recent advances have led to the development of novel therapeutic strategies, such as BCL-2 inhibitors (venetoclax), IDH1/2 inhibitors (ivosidenib, enasidenib), CD47 inhibitors (magrolimab), TIM-3 inhibitors (sabatolimab), XPO1 inhibitors (eltanexor), NEDD8-activating enzyme inhibitors (pevonedistat), TP53-targeted agents (eprenetapopt), liposomal chemotherapy (CPX-351), and oral HMA formulations. Combinations of hypomethylating agents with these new drugs, as first-line treatment, have to date not proven more efficacious than HMA monotherapy. This review summarizes the current therapeutic landscape on novel therapies for HR-MDS, highlighting their mechanism of action, efficacy, and demonstrates the unmet clinical need for more effective therapies."

Journal • Review • Acute Myelogenous Leukemia • Bone Marrow Transplantation • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • Transplantation • HAVCR2 • IDH1 • IDH2

Few Drug Approvals in MDS: Lessons and Insights from a Decade of Clinical Trials (ICKSH 2026) - "Aside from allogeneic transplantation, the current standard of care approach for higher -risk myelodysplastic syndromes/neoplasms (HR -MDS) remains monotherapy with a hypomethylating agent (HMA) including azacitidine, decitabine, or oral decitabine/cedazurid ine...In this lecture , I will discuss lessons learned from the recently reported negative trials of azacitidine in combination with eprenetapopt (APR -246), magrolimab, pevonedistat, sabatolimab, tamibarotene, and venetoclax...Instead, I will advocate for using the IWG 2023 response criteria to better capture clinically meaningful benefits in HR-MDS. Lastly, I will emphasize the need for the scientific community to access patient -level data and samples from failed phase 3 trials in an efficient and expedited fashion to inform the development of subsequent trials."

Clinical • Chronic Myelomonocytic Leukemia • Hematological Malignancies • Myelodysplastic Syndrome • TP53

The tumor microenvironment in leukemia: molecular pathways of immune evasion. (PubMed, Front Immunol) - "We further discuss implications for immunotherapy, noting that agents like magrolimab (anti-CD47) combined with azacitidine have demonstrated objective response rates (ORR) exceeding 80% in early-phase AML trials, though challenges such as on-target anemia persist. By integrating current evidence from preclinical metabolic profiling to Phase 3 clinical data on E-selectin inhibition (uproleselan)-we clarify the immune landscape of leukemia and outline avenues for innovative treatments. Ultimately, this Review underscores the need for multifaceted immunotherapeutic approaches that account for the complex interactions within the TME."

Biomarker • Journal • Review • Acute Myelogenous Leukemia • Chronic Lymphocytic Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

MORPHEUS mUC: Study Evaluating the Efficacy and Safety of Multiple Immunotherapy-Based Treatments and Combinations in Patients With Urothelial Carcinoma (MORPHEUS-UC) (clinicaltrials.gov) - P1/2 | N=272 | Completed | Sponsor: Hoffmann-La Roche | Active, not recruiting ➔ Completed

Trial completion • Bladder Cancer • Genito-urinary Cancer • Oncology • Solid Tumor • Urothelial Cancer • PD-L1

Atezolizumab Plus Magrolimab, Niraparib, or Tocilizumab in Platinum-Refractory Metastatic Urothelial Carcinoma: A Phase Ib/II Open-Label, Randomized Umbrella Study. (PubMed, Clin Cancer Res) - P1/2 | "The evaluated regimens in MORPHEUS-UC were tolerable. However, response rates for the combinations did not meet the criteria for further development in platinum-experienced locally advanced or mUC."

IO biomarker • Journal • Metastases • P1/2 data • Tumor mutational burden • Oncology • Solid Tumor • Urothelial Cancer • PD-L1 • TMB

IgG4 anti-CD47: Erythrophagocytosis and potential transfusion complications. (PubMed, Transfusion) - "IgG4 RBC antibodies, generally not considered clinically significant for transfusion, can result in erythrophagocytosis providing an explanation for anemia related to anti-CD47 mediated by FcγRI and FcγRIIa. Enhanced phagocytosis of alloantibody-coated RBCs with concurrent blocking CD47 suggests potential for enhanced complications for patients who develop RBC alloantibodies while receiving cancer therapies targeting CD47."

Journal • Hematological Disorders • Oncology

Phase 1b/2 Study of Magrolimab (Magro), Azacitidine (AZA) and Venetoclax (VEN) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High Risk Acute Myeloid Leukemia (AML) and Relapsed Refractory (R/R) AML: Final Clinical Data and Genomic Markers of Resistance/Relapse (ASH 2024) - "Interestingly, pts with TP53mut AML who underwent alloSCT had med EFS 12 mos and med OS NR. Potential mechanisms of resistance/relapse included erythroid differentiation, inflammatory tumor microenvironment, and CD47 upregulation."

Clinical data • P1/2 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Neutropenia • Oncology • CD47 • IFNG • TNFA • TP53

MAGROLIMAB (MAGRO) + AZACITIDINE (AZA) VS PLACEBO (PBO) + AZA IN PATIENTS (PTS) WITH UNTREATED HIGHER-RISK (HR) MYELODYSPLASTIC SYNDROMES (MDS): PHASE 3 ENHANCE STUDY FINAL ANALYSIS (EHA 2024) - P3 | "In the ENHANCE study, Magro+AZA did not meet the primary endpoint of OS and CRR and showed moresevere TEAEs overall, including a higher rate of Gr ≥3 TEAEs, in treatment-naïve pts with HR-MDS. Confounding factors, such as imbalance in pts eligible for transplant and a partial clinical hold duringenrollment, may limit data interpretation. Findings highlight challenges of developing anti-CD47 therapies andother new treatments in HR-MDS."

Clinical • P3 data • Acute Myelogenous Leukemia • Anemia • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • TP53

Clinical advances in CD47-SIRPα axis-targeted cancer immunotherapy: Mechanisms, strategies, challenges, and future perspectives. (PubMed, Biochem Biophys Res Commun) - "This challenge was underscored by a pivotal setback in the field: the Phase III trial of Magrolimab, the first anti-CD47 therapy to reach this stage, which failed to meet its primary endpoint and ultimately led to the discontinuation of its development program...Furthermore, we summarize the major clinical challenges, including safety concerns, resistance mechanisms, and diagnostic complexities. By synthesizing these key findings, this review provides valuable insights for optimizing future drug design, refining combination regimens, and guiding patient selection strategies, thereby offering a crucial reference for overcoming current limitations and fully realizing the therapeutic potential of this promising axis."

Journal • Review • Hematological Disorders • Hematological Malignancies • Oncology • Solid Tumor • SIRPA

Tolerability and efficacy of the first-in-class anti-CD47 antibody magrolimab combined with azacitidine in frontline TP53m AML patients: Phase 1b results. (ASCO 2022) - P1b, P3 | "In high-risk frontline TP53m AML pts unsuitable for intensive chemotherapy, magrolimab+AZA showed durable responses and encouraging OS in a single-arm study. A Phase 3 trial in TP53m AML (ENHANCE-2; NCT04778397) of this combination vs standard of care is ongoing."

Clinical • P1 data • Acute Myelogenous Leukemia • Anemia • Constipation • Cough • Fatigue • Febrile Neutropenia • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Thrombocytopenia • TP53

Nature of Clinical Response and Depth of Molecular Response in Patients with TP53 Mutant Myelodysplastic Syndromes (MDS) and Acute Myeloid Leukemia (AML) Treated with Magrolimab with Azacitidine (ASH 2022) - P1b | "In AML, VAF 0.10 at all timepoints. Conclusions In this phase 1b study, magrolimab demonstrated a reduction in the allele frequency of TP53 mutations as early as cycle 3 in patients with MDS or AML treated with magrolimab + azacitidine, potentially altering the course of disease in patients with TP53-mutated malignancies."

Clinical • Acute Myelogenous Leukemia • Hematological Malignancies • Leukemia • Myelodysplastic Syndrome • Oncology • ASXL1 • CALR • DNMT3A • NRAS • RUNX1 • TET2 • TP53

Magrolimab in combination with azacitidine for untreated higher-risk myelodysplastic syndromes (HR-MDS): 5F9005 phase 1b study results. (ASCO 2022) - P1b, P3 | "Magrolimab+AZA was well tolerated with promising efficacy in pts with untreated HR-MDS including those with TP53-mut and TP53-wt disease. A Phase 3 trial of magrolimab/placebo+AZA (ENHANCE: NCT04313881) is ongoing."

Combination therapy • P1 data • Anemia • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Neutropenia • Oncology • Thrombocytopenia • CD47 • TP53

Phase I/II Study of Azacitidine (AZA) with Venetoclax (VEN) and Magrolimab (Magro) in Patients (pts) with Newly Diagnosed (ND) Older/Unfit or High-Risk Acute Myeloid Leukemia (AML) and Relapsed/Refractory (R/R) AML (ASH 2022) - P1/2, P3 | "The triplet combination of AZA VEN Magro appears safe with encouraging CR rates in a cohort of ND pts with 93% adverse risk ELN and 71% with adverse cytogenetic features. Responses in R/R AML were modest with prior VEN exposed pts faring poorly. Further trial enrollment and correlative analysis is underway and a phase III placebo controlled, randomized, international study to evaluate this triplet in ND AML has been initiated (ENHANCE-3, NCT05079230)."

Clinical • P1/2 data • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Malignancies • Hepatology • Idiopathic Arthritis • Infectious Disease • Neutropenia • Pneumonia • Respiratory Diseases • Transplantation • TP53

MAGROLIMAB VS PLACEBO IN COMBINATION WITH VENETOCLAX AND AZACITIDINE IN PREVIOUSLY UNTREATED PATIENTS WITH ACUTE MYELOID LEUKEMIA WHO ARE INELIGIBLE FOR INTENSIVE CHEMOTHERAPY: THE ENHANCE-3 STUDY (EHA 2024) - P3 | "In pts with newly diagnosed AML ineligible for intensive chemotherapy, Magro + VEN + AZA did not improveOS or CR, with a higher incidence of fatal AEs occurring in pts treated with Magro. The study was stopped earlyas the prespecified futility boundary for OS (HR, 1. 1) was crossed."

Clinical • Combination therapy • Acute Myelogenous Leukemia • Anemia • Bone Marrow Transplantation • Febrile Neutropenia • Hematological Disorders • Hematological Malignancies • Infectious Disease • Leukemia • Neutropenia • Oncology • Transplantation • TP53

Phase 2 Multi-Arm Study of Magrolimab Combinations in Patients With Acute Myeloid Leukaemia. (PubMed, EJHaem) - P2 | "This phase 2 study evaluated magrolimab+venetoclax (VEN)+azacitidine (AZA) in untreated, unfit acute myeloid leukaemia (AML) and magrolimab+mitoxantrone+etoposide+cytarabine in relapsed/refractory (R/R) AML. Magrolimab was safely combined with existing AML therapies with no new safety signals. This trail was registered at www.clinicaltrials.gov as NCT04778410."

Journal • P2 data • Acute Myelogenous Leukemia • Hematological Disorders • Hematological Malignancies • Leukemia • Oncology

Magrolimab in Combination With Azacitidine in Patients With Higher-Risk Myelodysplastic Syndromes: Final Results of a Phase Ib Study. (PubMed, J Clin Oncol) - P1b, P3 | "Magrolimab + azacitidine was well tolerated with promising efficacy in patients with untreated higher-risk MDS, including those with TP53 mutations. A phase III trial of magrolimab/placebo + azacitidine is ongoing (ENHANCE: NCT04313881)."

Combination therapy • Journal • P1 data • Bone Marrow Transplantation • Constipation • Gastroenterology • Gastrointestinal Disorder • Hematological Disorders • Hematological Malignancies • Myelodysplastic Syndrome • Oncology • Thrombocytopenia • Transplantation • TP53