Ficlatuzumab Plus Chemotherapy Produces Promising Preliminary Clinical Activity in High-Risk AML


The investigational therapy ficlatuzumab in combination with cytarabine demonstrated encouraging clinical efficacy with favorable tolerability when used as a treatment in patients with high-risk acute myeloid leukemia.

Charalambos Andreadis, MD

Charalambos Andreadis, MD

The investigational therapy ficlatuzumab (formerly AV-299) in combination with cytarabine demonstrated encouraging clinical efficacy with favorable tolerability when used as a treatment in patients with high-risk acute myeloid leukemia (AML), according to preliminary data from a phase 1b trial (NCT02109627) published in Blood Cancer Discovery.1

Results from the study showed that the overall response rate (ORR) achieved with the combination was 53% (n = 9/17), which was comprised entirely of complete remissions (CRs). Additionally, of the 9 patients who responded to treatment with the regimen, 4 achieved minimal residual disease (MRD) negativity.

The median progression-free survival (PFS) and overall survival in all patients was 6.6 months and 18.1 months, respectively. The median PFS reported in responders was higher, at 31.2 months; the median OS had not yet been reached in this subgroup.

“The 53% response rate was quite striking to us since historical response rates for the standard-of-care treatment are [around] 30% ,” lead study author Charalambos Andreadis, MD, professor of clinical medicine at the University of California, San Francisco, stated in a press release. “Although 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.”

Currently, the standard induction therapy for patients with AML who have a good performance status is comprised of an anthracycline and cytarabine, referred to as the 7+3 regimen. Although some patients are able to experience CRs with this approach, 20% to 40% will not respond to this approach or will relapse after treatment. Allogeneic hematopoietic cell transplant (HCT) continues to represent the option with greatest curative potential in this population. An unmet need for novel treatment approaches to improve outcomes remains.

Previously, data from retrospective series have indicated that high serum hepatocyte growth factor (HGF) is linked with more aggressive disease and worse survival in patients with AML. The first-in-class monoclonal antibody ficlatuzumab binds extracellular HGF to prevent it from activating MET signaling and stimulating tumor growth. As such, investigators hypothesized that the addition of the agent to high-dose cytarabine could improve outcomes for this patient population.

The key objectives of the trial were to examine the safety and maximum-tolerated dose of ficlatuzumab. Important secondary objectives included identifying the rate of overall and CR and PFS. Other exploratory objectives examined OS and biomarker changes throughout the course of treatment.

To be eligible for enrollment, patients had to be at least 18 years of age and have histologically confirmed relapsed or refractory AML. Notably, patients could not have received more than 2 previous cycles of AML-directed treatment; one of these cycles had to be an anthracycline and cytarabine combination. All participants had a documented ejection fraction that was greater than 40% and acceptable organ function.

Study participants received 4 doses of intravenous ficlatuzumab every 14 days, on days 0, 14, 28, and 42, plus cytarabine. Cohort 1 received ficlatuzumab at a dose of 10 mg/kg, cohort 2 received the escalated dose of 15 mg/kg, and cohort 3 received the agent at the highest dose of 20 mg/kg. Additionally, fixed-dose cytarabine was given at 2,000 mg/m2 daily; this was started 48 hours after the first dose of ficlatuzumab for 5 days thereafter for all dose levels.

Among 17 evaluable patients, the median age was 58 years (range, 22-74), with 76.5% of patients under the age of 65 years. Moreover, 58.8% were male, all had an ECOG performance status of 1 or less, 76.5% had de novo disease at diagnosis, and all were primary refractory. Moreover, 70.6% of patients were poor risk, 23.5% were intermediate risk, and 5.9% were favorable risk. Additionally, 41.2% of patients had a complex karyotype, 29.4% had a normal karyotype, 23.5% had 5q deletion, and 5.9% had a monosomal karyotype. The most prevalent mutations among patients were IDH1 and IDH2 (17.6%).

Overall, 65% of patients completed all planned treatment on the study. Ten patients, 8 of whom achieved a CR, and 2 who did not, also went on to receive HCT, and 6 remain in full remission.

No protocol-defined dose-limiting toxicities were reported, and the 20 mg/kg dose was selected for the dose-expansion cohort.

In terms of safety, the most common grade 3 or higher adverse effect (AE) was febrile neutropenia (53%). Other common grade 3 or higher AEs included sepsis (17%), esophagitis/ulcers (12%), GIB (12%), and hypotension (12%).

“Together, our findings suggest that targeting an extracellular factor in conjunction with existing cancer therapies could be an effective therapeutic strategy for AML treatment,” Andreadis concluded.


  1. Wang VE, Blaser BW, Patel RK, et al. Inhibition of MET signaling with ficlatuzumab in combination with chemotherapy in refractory AML: clinical outcomes and high-dimensional analysis. Blood Cancer Discov. Published online on July 16, 2021. doi:10.1158/2643-3230.BCD-21-0055
  2. Ficlatuzumab plus chemotherapy shows promise for the treatment of patients with relapsed/refractory acute myeloid leukemia. News release. AACR. July 16, 2021. Accessed July 19, 2021.
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