First-in-Human Study Finds FF-10101-01 Has Clinical Activity in Relapsed/Refractory FLT3-Mutated AML

For patients with relapsed and/or refractory FLT3-mutated acute myeloid leukemia (AML), treatment with the selective and irreversible FLT3 inhibitor FF-10101-01 had promising clinical activity. This is according to findings from a first-in-human study presented at the 2021 ASCO Annual Meeting.

“FF-10101-01 is highly active against FLT3-ITD mutations associated with high relapse and low survival/remission rates, as well as resistance-conferring D835 and F691 tyrosine kinase domain (TKD) and non-canonical FLT3 activating mutations,” the investigators, led by Mark J. Levis, MD, PhD, of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, wrote.

A total of 52 patients with a median age of 61 years (range = 21-84) were enrolled in the phase I dose-escalation trial. Participants had received a median of three prior therapies (range = 0-6). The most commonly observed mutations were FLT3-ITD mutations (42%), followed by FLT3-TKD mutations (10%), and both FLT3-ITD and FLT3-TKD mutations (2%). Most patients (82%) with known FLT3 mutations had previously received FLT3 inhibitors, the authors observed.

To establish the maximum tolerated dose, patients were randomized to receive continuous FF-10101-01 at either:

  • 10-225 mg once daily
  • 50-100 mg every other day

Treatment continued until unacceptable toxicity or no further clinical benefit was observed, for a median of 5.7 weeks (range = 0.1-36).

Common adverse events related to FF-10101-01 included nausea, diarrhea, elevated creatine kinase, vomiting, and increased aspartate aminotransferase. At a dosage of 75 to 150 mg/day, grade 3/4 differentiation syndrome was observed in 8% of patients (n=4). When total daily doses exceeded 200 mg/day, cardiac events (heart failure with reduced ejection fraction; grade 3 increased troponin/creatine kinase) were noted as dose-limiting toxicities.

During follow-up, five of 31 patients evaluable for response experienced a complete remission (CR), for a CR rate of 16%. Two patients, including one whose disease had previously progressed despite treatment with gilteritinib, experienced CR with incomplete hematologic recovery at a dose of 50 mg every other day. Another two patients achieved CR with incomplete platelet recovery at 50 and 100 mg, respectively, every other day; and one patient with a FLT3-ITD mutation achieved a CR at 75 mg every other day.

An additional two patients experienced a partial response (defined as a ≥50% decrease in bone marrow blasts to 5-25% abnormal cells) at total daily doses of 50 and 150 mg, respectively. Both patients had previously received FLT3 kinase inhibitors, and two had FLT3-ITD mutations.

The median time to response was 13.3 weeks, the researchers added.

“Doses of FF-10101-01 50 to 75 mg every other day were well tolerated and resulted in sustained FLT3 inhibition,” the authors wrote. Based on further review of data, they added, the recommended phase II dose will be 50 or 75 mg every other day. At a dose of 75 mg every other day, trough plasma concentrations were >90 ng/mL and p-FLT3 inhibition was maintained over the dosing interval in >90% of patients.

The findings of this early-phase study need to be confirmed in larger trials, the authors noted, but they concluded that FF-10101-01 is a promising investigational therapy for AML.

The authors report relationships with Fujifilm Pharmaceuticals, which funded the trial.


Levis MJ, Smith C, Perl AE, et al. Phase 1 first-in-human study of irreversible FLT3 inhibitor FF-10101-01 in relapsed or refractory acute myeloid leukemia. Abstract #7008. Presented at the 2021 American Society of Clinical Oncology Annual Meeting, June 4-8, 2021.