A better FLT3 inhibitor for AML?

Response and survival

Among the 127 patients who were FLT3-positive, the ORR was 52% (n=66). The complete response (CR) rate was 6.3% (n=8). The composite CR rate, which includes CRs with incomplete hematologic recovery (CRi) and incomplete platelet recovery (CRp), was 40.9% (n=52). And the partial response (PR) rate was 11% (n=14).

“As we scale up the dose, the PRs shift on over to CRis, and the dominant response is, in fact, a complete response with incomplete count recovery,” Dr Levis said. “The categories where we had the largest number of responses were the 120 mg and 200 mg categories. We didn’t really have enough patients in the 300 mg category to comment on it. ”

For the FLT3-positive patients, the median duration of response was 126 days.

“The duration of response really stood out here,” Dr Levis said. “It’s over 4 months. That is something we really didn’t see with the other drugs, and I suspect that is a reflection of the suppression of the outgrowth of these resistance mutations.”

Unfortunately, FLT3-wild-type patients did not fare as well. The ORR among these patients was 8.8%. None of the patients achieved a CR, 3 had a composite CR (5.3%), and 2 had a PR (3.5%).

Among the FLT3-positive patients, the median overall survival was about 27 weeks. It was 128 days in the 20 mg dose cohort (n=13), 105.5 days in the 40 mg cohort (n=8), 201 days in the 80 mg cohort (n=12), 199 days in the 120 mg cohort (n=40), and 161 days in the 200 mg cohort (n=45). Dr Levis did not present survival data for the 300 mg or 450 mg cohorts, which included 7 and 2 patients, respectively.

“[Relapsed/refractory AML] is a population that has a median survival of about 3 months with conventional therapy, at least by historical publications,” Dr Levis noted. “If you look at survival in this trial, patients treated at the FLT3-inhibitory doses [had a] greater than 6-month median survival.”

He added that studies of ASP2215 in combination with other agents are ongoing in patients with newly diagnosed AML. And phase 3 trials of ASP2215 at the 120 mg dose, with the option of scaling up to 200 mg, are planned.

*Information in the abstract differs from that presented at the meeting.