THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY MAGROLIMAB COMBINED WITH AZACITIDINE IS WELL-TOLERATED AND EFFECTIVE IN MDS PATIENTS: PHASE 1B RESULTS
Author(s): ,
Sallman David
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Monzr Al Malki
Affiliations:
City of hope,Duarte,United States
,
Adam Asch
Affiliations:
University of Oklahoma,Oklahoma City,United States
,
Daniel Lee
Affiliations:
Columbia University,New York,United States
,
Suman Kambhampati
Affiliations:
Healthcare Midwest,Kansas City,United States
,
Will Donnellan
Affiliations:
Sarah Cannon Research Institute,Tennessee,United States
,
Paresh Vyas
Affiliations:
University of Oxford,Oxford,United Kingdom
,
Daniel Pollyea
Affiliations:
University of Denver,Denver,United States
,
Terrence Bradley
Affiliations:
University of Miami,Miami,United States
,
Deepa Jeyakumar
Affiliations:
University of California Irvine,Irvine,United States
,
Guido Marcucci
Affiliations:
City of hope,Duarte,United States
,
Guillermo Garcia-Manero
Affiliations:
MD Anderson Cancer Center,Houston,United States
,
Rami Komrokji
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
Joanna Van Elk
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Ming Lin
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Roy Maute
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Jens-Peter Volkmer
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Chris Takimoto
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Mark Chao
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
Naval Daver
Affiliations:
MD Anderson Cancer Center,Houston,United States
EHA Library. David S. 06/12/20; 295007; S187
Sallman David
Sallman David
Contributions
Abstract

Abstract: S187

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Novel treatments for MDS II

Background
Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and don’t eat me signal on cancers.  It induces tumor phagocytosis and eliminates leukemia stem cells.  Azacitidine (AZA) synergizes with magrolimab by inducing eat me signals on leukemic blasts, enhancing phagocytosis.   We report here Ph1b data of magrolimab in combination with AZA for untreated higher risk MDS, a potential registrational cohort. 

Aims

The aims of this Ph1b study are to determine the safety and efficacy of magrolimab + AZA in untreated higher risk MDS patients.

Methods
Magrolimab + AZA was given to untreated intermediate to very high risk IPSS-R MDS patients. A magrolimab priming/intrapatient dose escalation regimen (1-30 mg/kg QW, Q2W Cycle 3+) was used.  AZA was dosed 75mg/m2 on days 1-7. Efficacy was assessed by IWG 2006 criteria.  

Results
39 MDS patients with a median age of 70 years (range 47 – 80) were treated with magrolimab + AZA.  28% were intermediate cytogenetic risk with 64% poor risk (8% unknown/missing).  31% were therapy-related MDS and 13% of all patients were TP53 mutant.  The combo was well tolerated with safety similar to AZA alone. Common treatment-related AEs or AEs of interest were anemia (44%), fatigue (18%), infusion reaction (18%), neutropenia (8%) and thrombocytopenia (5%).  No treatment-related febrile neutropenia was observed.  In addition, no patients discontinued due to an AE. On target anemia was mostly mild, transient and mitigated by the priming dose regimen with many patients decreasing RBC transfusion requirements on therapy.  The mean drop in hemoglobin with the first dose of magrolimab + AZA was only 0.4 g/dL.  In RBC transfusion dependent patients, 58% of patients became transfusion independent.  In 33 efficacy evaluable patients, 30 (91%) had an objective response (42% CR, 24% marrow CR (4/8 also with HI), 3% PR, 21% HI alone, 9% SD).  MDS patient responses deepened over time, with a 56% CR rate in patients with ≥ 6 mo follow-up.  Cytogenetic CRs were seen in 35% of evaluable responding patients. 22% of patients with CR/CRi/marrow CR were MRD negative by multiparameter flow cytometry.  Median time to initial response was rapid at 1.9 months, faster than expected with AZA alone. Median duration of response has not been reached, with a median follow-up of 5.8 mos (range: 2 – 15 mos).  91% of responding patients continue in response at 6 mos.   The median overall survival has also not been reached (range 1.4 – 18.3 mos ongoing) with a 6 mo overall survival estimate of 100%.

Conclusion
Magrolimab is a novel macrophage targeting immunotherapy that with AZA is well tolerated with durable efficacy in MDS.  A potential registration single arm MDS cohort is ongoing (NCT03248479).  ENHANCE, a randomized Ph3 MDS trial of magrolimab + AZA vs. AZA is being initiated. Additional patients, follow up and translational analyses will be reported at time of presentation. Funded by Forty Seven and the California Institute for Regenerative Medicine.   

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Immunotherapy, Leukemic stem cell, Macrophage, MDS

Abstract: S187

Type: Oral Presentation

Presentation during EHA25: All oral abstract presentations will be made available on the on-demand Virtual Congress platform as of Friday, June 12 at 08:30 CEST and will be accessible until October 15, 2020.

Session title: Novel treatments for MDS II

Background
Magrolimab (Hu5F9-G4) is an antibody blocking CD47, a macrophage immune checkpoint and don’t eat me signal on cancers.  It induces tumor phagocytosis and eliminates leukemia stem cells.  Azacitidine (AZA) synergizes with magrolimab by inducing eat me signals on leukemic blasts, enhancing phagocytosis.   We report here Ph1b data of magrolimab in combination with AZA for untreated higher risk MDS, a potential registrational cohort. 

Aims

The aims of this Ph1b study are to determine the safety and efficacy of magrolimab + AZA in untreated higher risk MDS patients.

Methods
Magrolimab + AZA was given to untreated intermediate to very high risk IPSS-R MDS patients. A magrolimab priming/intrapatient dose escalation regimen (1-30 mg/kg QW, Q2W Cycle 3+) was used.  AZA was dosed 75mg/m2 on days 1-7. Efficacy was assessed by IWG 2006 criteria.  

Results
39 MDS patients with a median age of 70 years (range 47 – 80) were treated with magrolimab + AZA.  28% were intermediate cytogenetic risk with 64% poor risk (8% unknown/missing).  31% were therapy-related MDS and 13% of all patients were TP53 mutant.  The combo was well tolerated with safety similar to AZA alone. Common treatment-related AEs or AEs of interest were anemia (44%), fatigue (18%), infusion reaction (18%), neutropenia (8%) and thrombocytopenia (5%).  No treatment-related febrile neutropenia was observed.  In addition, no patients discontinued due to an AE. On target anemia was mostly mild, transient and mitigated by the priming dose regimen with many patients decreasing RBC transfusion requirements on therapy.  The mean drop in hemoglobin with the first dose of magrolimab + AZA was only 0.4 g/dL.  In RBC transfusion dependent patients, 58% of patients became transfusion independent.  In 33 efficacy evaluable patients, 30 (91%) had an objective response (42% CR, 24% marrow CR (4/8 also with HI), 3% PR, 21% HI alone, 9% SD).  MDS patient responses deepened over time, with a 56% CR rate in patients with ≥ 6 mo follow-up.  Cytogenetic CRs were seen in 35% of evaluable responding patients. 22% of patients with CR/CRi/marrow CR were MRD negative by multiparameter flow cytometry.  Median time to initial response was rapid at 1.9 months, faster than expected with AZA alone. Median duration of response has not been reached, with a median follow-up of 5.8 mos (range: 2 – 15 mos).  91% of responding patients continue in response at 6 mos.   The median overall survival has also not been reached (range 1.4 – 18.3 mos ongoing) with a 6 mo overall survival estimate of 100%.

Conclusion
Magrolimab is a novel macrophage targeting immunotherapy that with AZA is well tolerated with durable efficacy in MDS.  A potential registration single arm MDS cohort is ongoing (NCT03248479).  ENHANCE, a randomized Ph3 MDS trial of magrolimab + AZA vs. AZA is being initiated. Additional patients, follow up and translational analyses will be reported at time of presentation. Funded by Forty Seven and the California Institute for Regenerative Medicine.   

Session topic: 10. Myelodysplastic syndromes - Clinical

Keyword(s): Immunotherapy, Leukemic stem cell, Macrophage, MDS

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