Lefacizumab (AK117) ORR reaches 80%! Clinical data on the combined treatment of phase II
On May 14th, Kangfang Biotechnology announced that its independently developed new generation anti-CD47 humanized IgG4 monoclonal antibody, Lefacizumab (AK117), combined with Azacitidine+Vinaccra, is a randomized, double-blind, controlled phase II study (AK117-206) for the treatment of previously untreated acute myeloid leukemia (AML) that is not suitable for intensified chemotherapy. The study will be presented orally at the 2026 European Hematology Association (EHA) Annual Meeting.
The research data confirms that the combination therapy of leflunomib has achieved a dual breakthrough in efficacy and safety, providing potential better treatment options for refractory AML patients worldwide.
Indications clinical dilemma
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, characterized by high malignancy, rapid progression, and poor prognosis. According to the NCCN guidelines, the ability to tolerate intensified induction chemotherapy is the core boundary for treatment decision-making.
For newly diagnosed AML patients who are elderly, frail, or have severe complications that prevent them from receiving intensive therapy, the combination of VEN and Azacitidine (VEN+AZA) is a globally recognized standard first-line regimen, but there are still significant limitations: overall response rate is insufficient, response duration is short, recurrence rate is high, median overall survival is only about 1 year, and long-term survival benefits are limited.
There is an urgent need in clinical practice for a new combination therapy that can further improve the depth of remission, prolong survival, and have controllable safety on the basis of standard protocols. The emergence of leflunomib is precisely to fill this huge unmet need.
Drug mechanism and clinical data
Lefacizumab is a new generation CD47 targeted antibody independently developed by Kangfang Biotechnology. It specifically blocks the binding of the “don’t eat me” signal CD47 and its receptor SIRP α on the surface of tumor cells, relieves immune suppression, activates macrophages to phagocytose leukemia cells, and achieves sustained clearance of tumors from the immune layer. Its unique molecular design prevents it from causing red blood cell agglutination, and its safety is significantly better than early CD47 antibodies.
The Phase II study results released by EHA show that the combination of leflunomib and VEN+AZA has outstanding therapeutic effects: the objective response rate (ORR) is 80.0%, which is higher than the control group’s 66.7%; The composite complete response rate (CRc) was 56.7%, which was better than the control group’s 53.3%; The proportion of CRc and MRD negative increased to 46.7%, significantly higher than the control group’s 36.7%, indicating deeper molecular remission.
The survival benefit was more significant. At a median follow-up of 8.84 months, the median overall survival (mOS) of the experimental group had not yet reached, while the control group was 8.3 months; The 9-month OS rate reached 78.7%, while the control group only had 43.1%. The median CRc duration was 10.4 months, far exceeding the control group’s 6.5 months.
In terms of safety, the incidence of adverse events in the two groups is comparable, and hematological toxicity such as anemia is controllable. No new safety signals have emerged, supporting long-term clinical application. Previously, Leflunomib has been granted orphan drug status for AML by the FDA and its clinical value has been internationally recognized.
CD47 target undergoes ups and downs
CD47, as a core target of the “don’t eat me” signaling pathway, was once regarded as the next generation immune star target. However, the early representative drug magrolimab failed in phase III research, leading to a cooling of global research and development. Against the backdrop of overall caution in the industry, Kangfang Biotechnology has achieved a breakthrough through better molecular design, higher safety, and more precise joint strategies.
At present, there are only a few companies globally that insist on advancing the CD47 track. Lefacizumab is the world’s first CD47 monoclonal antibody to enter phase III clinical registration for solid tumors, and has the most comprehensive layout in the field of hematological malignancies. Compared with similar products, Leflunomib has three core advantages:
No risk of red blood cell agglutination, lower hematological toxicity;
The combined VEN+AZA regimen showed survival benefits in a randomized controlled study;
Covering multiple indications for hematological malignancies such as AML and MDS, with solid clinical data.
Domestic drugs targeting the same target are mostly in early clinical stages, and Leflunomib has formed a clear leading advantage, becoming the most promising product in the global CD47 track.
