Novel SYK inhibitor shows ‘good early evidence’ of activity

Episodes of neutropenia and thrombocytopenia occurred in 1 patient each, and both were grade 1.

“So [TAK-659] seems quite well tolerated in that regard as well,” Dr Petrich observed.

The plasma profile on days 1 and 15 of cycle 1 indicate that PK steady-state conditions are generally achieved by day 8, with moderate accumulation after repeated, once-daily dosing for 15 days.

Antitumor activity

Of the 12 evaluable patients, 5 had tumor shrinkage at the 60, 80, or 100 mg dose levels. Three of the 6 DLBCL patients experienced tumor shrinkage, and there were “2 dramatic responses in patients with follicular lymphoma, including 1 CR [complete response],” Dr Petrich said.

One of these FL patients had an aggressive phenotype and never had a previous response last longer than 20 months.

“[H]e actually achieved a CR within 2 cycles—a dramatic response for his disease—and he remains on treatment, and he’s up to cycle 5 now,” Dr Petrich said.

The team concluded that the PK data support daily dosing, despite lower clearance than originally predicted.

“[There is] good early evidence of antitumor activity and no significant safety signals,” Dr Petrich said. “And the [hematologic] toxicity profile, in particular, seems to suggest this is a well-tolerated drug.”

The investigators are conducting expansion cohorts and are considering future combination studies. They recently activated a study in acute myeloid leukemia because TAK-659 has FLT3 inhibitory properties.  

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