THE FIRST-IN-CLASS ANTI-CD47 ANTIBODY HU5F9-G4 IS ACTIVE AND WELL TOLERATED ALONE OR IN COMBINATION WITH AZACITIDINE IN AML AND MDS PATIENTS: INITIAL PHASE 1B RESULTS
Author(s): ,
David Sallman
Affiliations:
Moffitt Cancer Center,Tampa,United States
,
William Donnellan
Affiliations:
Sarah Cannon Research Institute,Nashville,United States
,
Adam Asch
Affiliations:
University of Oklahoma,Oklahoma City,United States
,
Daniel Lee
Affiliations:
Columbia University,New York,United States
,
Monzr Al Malki
Affiliations:
City of Hope,Duarte,United States
,
Daniel Pollyea
Affiliations:
University of Colorado,Denver,United States
,
Suman Kambhampati
Affiliations:
Healthcare Midwest,Kansas City,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
,
Balaji Agoram
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
James Chen
Affiliations:
Forty Seven, Inc.,Menlo Park,United States
,
Jens 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
Paresh Vyas
Affiliations:
University of Oxford,Oxford,United Kingdom
EHA Library. Sallman D. Jun 15, 2019; 267461; S878
David Sallman
David Sallman
Contributions
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Abstract

Abstract: S878

Type: Oral Presentation

Presentation during EHA24: On Saturday, June 15, 2019 from 16:30 - 16:45

Location: Elicium 2

Background
Novel and effective therapies are needed in patients with myeloid malignancies. Hu5F9-G4 (5F9) is a first-in-class antibody targeting CD47, a macrophage immune checkpoint and “don’t eat me” signal on cancers, that induces tumor cell phagocytosis.  CD47 is also a leukemia stem cell (LSC) marker in AML.   Pre-clinically, CD47 blockade induces phagocytosis of AML cells and eliminates LSCs in animal models.  Azacitidine (AZA) synergizes with 5F9 to eliminate AML by inducing pro-phagocytic signals on AML, thus enhancing phagocytosis.  This trial clinically investigated 5F9 alone or with AZA in AML/MDS patients and is the first report of a clinical study combining a CD47 targeting agent with a hypomethylating/cytotoxic agent. 

Aims
The primary objectives of this study were to evaluate the safety and efficacy of 5F9 treatment in relapsed/refractory (r/r) AML/MDS and 5F9 in combination with AZA in untreated AML and MDS patients.

Methods
This Phase 1b trial enrolled: 1) relapsed/refractory (r/r) AML/MDS patients with 5F9 alone; and 2) untreated AML (induction ineligible) and intermediate-very high risk MDS patients with 5F9+AZA. A 5F9 priming/intra-patient dose escalation regimen (1-30 mg/kg weekly) was used to mitigate on-target anemia.  Standard AZA dosing was used.   

Results
10 (6 AML, 4 MDS) r/r pts received 5F9 (median 2 prior therapies (range 1-6).  24 untreated pts (15 AML, 9 MDS) received 5F9+AZA.  In total, median age was 73, 62% of AML pts were intermediate or poor cytogenetic risk (38% unknown), all MDS pts were intermediate or high risk by IPSS-R. 5F9 alone or with AZA was w­­­ell-tolerated with no MTD reached.  5F9 did not potentiate AZA toxicities. Treatment-related AEs (>10% of pts) for 5F9+AZA were anemia (25%), thrombocytopenia (20%), and infusion reactions (15%). In 25 efficacy evaluable pts, 8/15 (53%) untreated AML/MDS pts had a CR/CRi to 5F9+AZA (5/10 (50%) in AML, 3/5 (60%) in MDS).  1/10 (10%) r/r AML/MDS pts had a response (MLFS) to 5F9 alone.  LSCs were reduced/eliminated in the majority of 5F9+AZA responders. 50% of all responders were minimal residual disease (MRD) negative by flow cytometry.  4/10 (40%) previously red cell dependent AML pts became RBC transfusion independent and 4/5 (80%) MDS pts had hematologic improvement.  Time to response was more rapid (median 1.9 mos) than expected for AZA alone. As of Jan 2019, no responder has relapsed (median follow-up of 3.4 mos (range 1.1 – 6.8 mos). 2 pts had successful allogeneic transplant.  Additional patients and follow up will be reported.

Conclusion
5F9+AZA is a novel immunotherapy blocking a key macrophage/cancer checkpoint. It is well tolerated with promising activity in AML/MDS patients including rapid CRs with MRD negativity. Adding 5F9 to cytotoxic agents may be a promising treatment strategy.  An expansion cohort is ongoing (NCT03248479).  Funded by Forty Seven and California Institute for Regenerative Medicine.

Session topic: 4. Acute myeloid leukemia - Clinical

Keyword(s): Acute myeloid leukemia, Immunotherapy

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