Tolinapant receives orphan drug designation from the FDA for the treatment of T-cell lymphoma

On August 31, 2020, the U.S. Food & Drug Administration (FDA) granted orphan drug designation to tolinapant (formerly ASTX660) for the treatment of T-cell lymphoma.¹

Tolinapant is an orally administered, dual antagonist of the cellular inhibitor of apoptosis proteins 1 and 2 (cIAP-1 and cIAP-2) and the X-linked inhibitor of apoptosis protein (XIAP).

Tolinapant is currently under evaluation in a phase I/II study (NCT02503423). The phase I portion of the study aimed to determine the maximum tolerated dose (MTD), the recommended phase II dose (RP2D), and the safety of the drug at the RP2D. Tolinapant was orally administered once per day, on a 1-week-on/1-week-off schedule during 28-day cycles. The observed MTD was 210 mg/day and the RP2D was set at 180 mg/day. Tolinapant was generally well tolerated at doses ≤ 180 mg/day with no drug-related Grade ≥ 3 adverse events (AEs) at this dose level, and with the most common drug-related AEs being nausea (22%), pruritus (18%), and vomiting (18%).²

Preliminary results from the ongoing phase II of the study showed evidence of the clinical activity of tolinapant in a patient with cutaneous T-cell lymphoma.² The final results of the phase II part of the study remain unpublished.