CD47 Antibody Combo Shows Meaningful Activity in Previously Untreated AML

Combining the investigational anti-CD47 antibody AK117 with azacitidine (Vidaza) and venetoclax (Venclexta) demonstrated meaningful activity vs placebo plus azacitidine/venetoclax among patients with previously untreated acute myeloid leukemia (AML) who were ineligible for intensive chemotherapy, according to findings from a phase 2 trial (NCT06387420) presented at the European Hematology Association (EHA) 2026 Congress.¹

Data showed an overall response rate (ORR) of 80.0% (95% CI, 61.4%-92.3%) in the AK117 arm compared with 66.7% (95% CI, 47.2%-82.7%) in the placebo arm. The composite complete response (CRc) rates were 56.7% (95% CI, 37.4%-74.5%) vs 53.3% (95% CI, 34.3%-71.7%) in each respective arm, and the minimal residual disease (MRD)–negative CRc rates were 46.7% (95% CI, 28.3%-65.7%) vs 36.7% (95% CI, 19.9%-56.1%). Additionally, the median duration of response (DOR) was 10.4 months (95% CI, 5.3-not evaluable [NE]) vs 5.6 months (95% CI, 3.8-6.8) in each arm.

After a median follow-up of 10.0 months in the AK117 arm and 8.8 months in the placebo arm, the median overall survival (OS) was not reached (NR; 95% CI, 9.1-NE) vs 8.3 months (95% CI, 7.5-NE) in each arm (HR, 0.46; 95% CI, 0.20-1.06). The OS rates in each arm were 83.3% (95% CI, 64.5%-92.7%) vs 73.2% (95% CI, 53.4%-85.6%) at 6 months and 78.7% (95% CI, 58.2%-89.9%) vs 43.1% (95% CI, 22.0%-62.6%) at 9 months. The median event-free survival (EFS) was 9.1 months (95% CI, 5.8-11.4) vs 6.9 months (95% CI, 4.2-8.2) in each arm (HR, 0.46; 95% CI, 0.22-0.94), with respective 6-month EFS rates of 67.8% (95% CI, 45.3%-82.6%) vs 55.5% (95% CI, 32.5%-73.4%) and 9-month rates of 53.2% (95% CI, 31.1%-71.2%) vs 14.1% (95% CI, 2.4%-35.5%).

“AK117 combined with [azacitidine/venetoclax] demonstrated clinically meaningful efficacy with improved response quality, durable remission, and favorable survival trends. All these efficiency benefits were achieved with a manageable and comparable safety profile,” study investigator Huafeng Wang, from The First Affiliated Hospital and Zhejiang University School of Medicine in Hangzhou, China, stated in the presentation. “This [study] supports AK117 as a promising addition to the [azacitidine/venetoclax] backbone, but it still needs further clinical development in this population.”

AK117 was engineered as a next-generation, humanized IgG4 monoclonal antibody directed towards CD47. Both arms of the agent bind to CD47 on the same red blood cell (RBC) in a way that precludes RBC bridging and hemagglutination due to unique binding geometry, necessitating a priming dose to manage anemia.²

In the phase 2 study, patients were randomly assigned 1:1 to receive AK117 plus azacitidine/venetoclax (n = 30) or placebo in combination with azacitidine/venetoclax (n = 30). Across each 4-week cycle, patients received AK117 or placebo at 20 mg/kg intravenously on day 1 every 2 weeks; venetoclax at 100 mg on day 1, 200 mg on day 2 of cycle, and 400 mg daily thereafter every 4 weeks; and azacitidine at 75 mg/m² subcutaneously on days 1 to 7 every 4 weeks.

The trial’s primary end points were safety and CRc rate per ELN 2022 criteria. Secondary end points included ORR, MRD-negative CRc, duration of CRc, EFS, and OS. Patients 18 years and older with newly diagnosed AML ineligible for intensive chemotherapy, an ECOG performance status of 3 or lower or 2 or lower if 75 years or older, and adequate organ function were eligible for enrollment on the trial.

The median patient age was 61.6 years (range, 23.7-74.4) in the AK117 arm and 64.0 years (range, 22.2-76.4) in the placebo arm; 50.0% vs 43.3% of patients in each arm were female. Most patients in each arm had an ECOG performance status of 2 (76.7% vs 83.3%), and favorable risk per ELN 2024 guidelines (50.0% vs 53.3%).

All patients experienced treatment-emergent adverse effects (TEAEs) of any grade. TEAEs of grade 3 or higher occurred in 96.7% of the AK117 arm and 93.3% of the placebo arm, and 66.7% vs 66.7% in each group experienced serious AEs. Three patients in the experimental arm discontinued treatment due to TEAEs compared with 2 in the placebo arm. Additionally, fatal TEAEs were reported in 16.7% and 30.0% of each respective arm. The most common TEAEs in the AK117 and placebo arms, respectively, included decreased platelet counts (86.7% vs 66.7%), decreased white blood cell counts (83.3% vs 83.3%), decreased absolute neutrophil counts (80.0% vs 76.7%), and anemia (46.7% vs 50.0%).

References

1. Jin J, Zhang L, Zhang Q, et al. A phase II randomized study of AK117 versus placebo in combination with venetoclax and azacitidine in previously untreated acute myeloid leukemia patients ineligible for intensive chemotherapy. Presented at: European Hematology Association 2026 Congress; June 11-14, 2026; Stockholm, Sweden. Abstract S131.
2. Qu T, Zhong T, Pang X, et al. Ligufalimab, a novel anti-CD47 antibody with no hemagglutination demonstrates both monotherapy and combo antitumor activity. J Immunother Cancer. 2022;10(11):e005517. doi:10.1136/jitc-2022-005517