Ficlatuzumab/Cytarabine Combination Yields Promising Results in Chemo-Refractory High-Risk Acute Myeloid Leukemia

Patients with chemotherapy-refractory, high-risk acute myeloid leukemia achieved promising benefit from treatment with ficlatuzumab and cytarabine.

Treatment with ficlatuzumab (previously AV-299) and cytarabine resulted in promising clinical activity in a population of patients with chemotherapy-refractory, high-risk acute myeloid leukemia (AML) and may have utility in conjunction with multiplexed single cell analyses to detect on-target activity, according to findings from a phase 1b trial (NCT02109627).

Investigators reported an overall response rate (ORR) of 53% (n= 9/17) based on bone marrow biopsy, all responses of which were complete responses (CR). A total of 16 patients were assessed for minimal residual disease (MRD) status, with 4 of 9 responders testing negative for MRD.

Trial eligibility required patients to be aged 18 years or older and have been diagnosed with histologically confirmed refractory AML or have relapsed within 12 months of their first CR/CR with incomplete hematologic recovery. Patients could not have received more than 2 cycles of AML-directed therapy, 1 of which needed to be an anthracycline/cytarabine combination.

The investigator-initiated trial utilized a 3+3 design, with patients being treated with 4 intravenous doses of ficlatuzumab every 14 days plus cytarabine. Dosage for ficlatuzumab started at 10 mg/kg in cohort 1, 15 mg/kg in cohort 2, and 20 mg/kg in cohort 3. Cytarabine was administered at a fixed dose of 2000 mg/m2 daily.

The primary outcome of the study was safety and determining the maximum tolerated dose of ficlatuzumab and cytarabine. Key secondary end points included ORR, CR rate, and progression-free survival (PFS), with exploratory end points including overall survival (OS) and biomarker changes over the course of treatment.

Investigators included 18 patients who consented from January 2014 to October 2018, 17 of whom enrolled on the study. One patient was excluded due to active fungal pneumonia.

Patients had a median age of 58 years (range, 22-74) and 4 patients were notably over 65 years of age. In total, 13 patients had de novo AML, 3 had secondary AML, and 1 had myelodysplastic syndrome, RAEB-2. Additionally, 41.2% of patients had a complex karyotype and 23.5% had a 5q deletion. Each dose escalation cohort had 3 patients enrolled. A total of 65% of patients completed all planned treatment doses of ficlatuzumab and no delay in administration was reported. Additionally, no dose-limiting toxicities were observed. The 20 mg/kg dose level of ficlatuzumab was selected for the dose expansion cohort.

The median time from the start and completion of treatment with ficlatuzumab to transplant were 107 days and 64 days, respectively. The most common conditioning regimen that was used was fludarabine and busulfan. Additionally, 60% of patients had matched unrelated donors, 40% had sibling donors, and 50% of donors were exact haplotype matches, 1 of whom was a sibling donor.

Additional findings from the study indicated that, as of censoring on June 30, 2020, patients had a median PFS of 6.6 months and a median OS of 18.1 months. Moreover, responders had a median PFS of 31.2 months and OS had not been reached. After censoring for hematopoietic cell transplant, the overall patient population had a median OS of 9.5 months and was not reached for responders.

In terms of safety, the most common grade 3 or higher adverse effect (AE) was febrile neutropenia (53%), with other AEs including sepsis (17%), esophagitis and ulceration (12%), gastrointestinal bleeding (12%), and hypotension (12%). Moreover, 12% of patients developed serious AEs. One death was reported on the study; the cause of death was sepsis, which was not believed to be related to treatment.


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 Can Disc. 2021;2(5):434-449. doi:10.1158/2643-3230.BCD-21-0055