Combination Ficlatuzumab and Cytarabine Show Clinical Activity in Relapsed/Refractory AML

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Despite advances in the treatment of acute myeloid leukemia (AML), only 29.5% of patients with the cancer are alive 5 years after diagnosis. Even with aggressive therapy, just 30% of patients achieve a complete remission with a median survival of 7.5 months, making it imperative to develop novel therapies to improve patient outcomes.

The results from a small phase Ib trial investigating ficlatuzumab, a first-in-class antihepatocyte growth factor (HGF) antibody, in combination with high-dose cytarabine for relapsed or refractory AML showed the doublet demonstrated clinical activity and a favorable safety profile. The study by Wang et al was published in Blood Cancer Discovery.

Study Methodology

Between 2014 and 2018, researchers enrolled 17 adult patients with AML that was either refractory to prior treatment or that had relapsed within 12 months of prior therapy. The patients received four doses of ficlatuzumab, administered 14 days apart, to target the MET axis in combination with high-dose cytarabine.

The primary objective of the study was to define the safety and the maximum tolerated dose of the combination regimen; the secondary objectives included determining the rate of overall and complete remission and progression-free survival. Exploratory objectives included assessing overall survival and biomarker changes throughout the treatment course.


The study found that 9 of the 17 patients (53%) experienced a complete response, and 4 of the responding patients had no signs of minimal residual disease. Among responding patients, the progression-free survival was 31.2 months, and the overall survival was not reached. Ten patients (8 responders and 2 nonresponders) proceeded to allogeneic hematopoietic cell transplantation; 6 of the patients remained in remission at the most recent follow-up.

The study results also showed that the most common adverse event with this therapy was febrile neutropenia. Serious adverse events occurred in two patients; there was one death reported deemed unrelated to the investigational therapy.


  • The investigational therapy ficlatuzumab, a first-in-class anti-HGF antibody, in combination with cytarabine demonstrated a favorable safety profile and promising signs of clinical efficacy in patients with relapsed/refractory AML.
  • The efficacy and safety of this treatment combination need to be validated in larger randomized trials.

To identify molecular changes associated with treatment response, the researchers analyzed peripheral blood mononuclear cells collected at baseline and at several timepoints after treatment initiation. They found that the ficlatuzumab treatment led to attenuated phosphorylation of MET, the receptor for HGF, thereby confirming on-target inhibition of HGF.

Clinical response to ficlatuzumab treatment was associated with reduced phosphorylation of the S6 protein and increased expression of genes involved in myeloid and leukocyte activation. Nonresponding patients were more likely to have increased expression of HGF; increased phosphorylation of S6; and expression of genes involved in protein translation, cell adhesion, and type I interferon signaling.

“The ficlatuzumab and cytarabine combination is well tolerated, with favorable efficacy. High-dimensional analyzes at single-cell resolution represent promising approaches for identifying biomarkers of response and mechanisms of resistance in prospective clinical studies,” concluded the study authors.

Clinical Significance

“The 53% response rate was quite striking to us since historical response rates for the standard-of-care treatment are in the 30% range,” said senior study author Charalambos Andreadis, MD, Professor of Clinical Medicine at the University of California, San Francisco, in a statement. “While these results need to be validated in a larger study, they suggest that ficlatuzumab in combination with single-agent chemotherapy may lead to better responses with less toxicity in patients with relapsed/refractory AML.”

Disclosure: Funding for this study was provided by the National Cancer Institute, the Damon Runyon Postdoctoral Award, the ASCO Young Investigator Award, the Department of Defense, and a Gateway for Cancer Grant. For full disclosures of the study authors, visit

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