Exploring Safety and Efficacy of 5F9 and Azacitidine in AML and MDS

Watch our interview with David Sallman, MD.

In initial results from a phase Ib trial presented at the 2019 American Society of Clinical Oncology annual meeting, the CD47-targeting antibody Hu5F9-G4 (5F9) induced responses in patients with acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), with or without the addition of azacitidine. Lead author David Sallman, MD, from the Moffitt Cancer Center in Tampa, Florida, added that this treatment approach was generally well tolerated, with no maximum tolerated dose reached.

David Sallman, MD
David Sallman, MD

By selectively targeting CD47 and “don’t-eat-me” signals on cancer cells, 5F9 induces tumor phagocytosis, Dr. Sallman explained to ASH Clinical News. “We know that azacitidine can upregulate pro ‘eat-me’ signals, and in an aggressive AML xenograft [preclinical] model, the combination of 5F9 and azacitidine significantly improved overall survival versus either azacitidine or 5F9 alone,” he added, describing the rationale behind this phase Ib study.

Per study protocol, patients with relapsed/refractory AML or MDS received treatment with 5F9 alone; patients with previously untreated AML or with higher-risk MDS received 5F9 in combination with azacitidine.

All participants received a 1 mg/kg priming dose of 5F9, and intrapatient dose escalation (1-30 mg/kg weekly) was used to mitigate on-target anemia.

As of May 10, 2019 (data cutoff date), 46 patients had been treated in the phase Ib portion of the trial, including 10 patients in the monotherapy group and 36 patients in the combination group. In the 5F9-alone group, patients had received a median of two prior therapies (range = 1-6).

Patients’ median age was 73 years (range not provided). Sixty-two percent of patients with AML had intermediate- or poor-risk cytogenetics, while all patients with MDS had high- or intermediate-risk disease. “More than half of AML patients had AML with myelodysplasia-related changes, so our treatment cohort consisted largely of older patients with an undertone of myelodysplasia,” Dr. Sallman noted.

5F9 alone or with azacitidine appeared to be well tolerated in this patient population, the investigators reported. Anemia was an expected adverse event (AE) of 5F9 treatment, and 25% of patients in the combination group experienced this AE, “predominantly in the first cycles,” Dr. Sallman noted. However, “fortunately, patients typically got back to their baseline hemoglobin levels at the end of the first treatment cycle … and hemoglobin improved over time.”

Other common treatment-related AEs included thrombocytopenia (20%) and infusion-related reactions (15%). “We also observed mild gastrointestinal side effects,” Dr. Sallman said, “but importantly, when 5F9 was combined with azacitidine, we saw no exacerbation of the monotherapy side effect profile, including no worsening of cytopenias.”

At the time of presentation, 25 patients were evaluable for response (10 with relapsed/refractory AML/MDS and 15 with untreated AML/MDS).

Eight of 15 patients (53%) with untreated AML/MDS who received 5F9 plus azacitidine experienced a complete response (CR) or CR with incomplete hematologic recovery. One of 10 patients (10%) with relapsed/refractory AML/MDS responded to 5F9 alone.

The investigators added that half of responders were measurable residual disease–negative by flow cytometry, and no responder had relapsed during a median follow-up of 3.4 months (range = 1.1-6.8 months).

“Even patients who had not objectively achieved a response remain on study treatment,” Dr. Sallman noted. “Follow-up is relatively short, and we’re hopeful that the [response] percentages may further increase over time as patients remain on study.” He added that expansion cohort studies also are being conducted.

The authors report relationships with Forty Seven, Inc., which sponsored the study.


Sallman DA, Donnellan WB, Asch AS, et al. The first-in-class anti-CD47 antibody Hu5F9-G4 is active and well tolerated alone or with azacitidine in AML and MDS patients: Initial phase 1b results. Abstract #7009. Presented at the 2019 ASCO Annual Meeting, June 3, 2019; Chicago, IL.