mycosis fungoides
Micrograph showing
The US Food and Drug Administration (FDA) has granted orphan drug designation to TTI-621 for the treatment of cutaneous T-cell lymphoma (CTCL).
TTI-621 is designed to activate the innate immune system by blocking the activity of CD47, a protein commonly found on the surface of cancer cells.
TTI-621 is a SIRPaFc fusion protein that consists of the CD47-binding domain of human SIRPa linked to the Fc region of a human immunoglobulin.
The drug is intended to act as a soluble decoy receptor, preventing CD47 from delivering its inhibitory signal, thereby enabling the activation of macrophage anti-tumor effects by pro-phagocytic signals.
TTI-621 is under investigation in a phase 1 trial of patients with relapsed/refractory solid tumors and CTCL (NCT02890368). Results from the dose-escalation portion of this study were presented at the 2017 ASH Annual Meeting (abstract 4076*).
The dose-escalation portion had a 3+3 design. TTI-621 was first given as a single intratumoral injection at 1 mg, 3 mg, or 10 mg. Then, it was given at 10 mg on Monday, Wednesday, and Friday for 1 week. Next, it was given on the same 3-day schedule for 2 weeks.
Results were reported for 18 patients, 56% of whom were male. They had a median age of 69 (range, 32-85) and a median number of 3 prior therapies (range, 1-16), including radiation (39%).
Eleven patients had CTCL, and 10 were evaluable. Researchers said they observed “rapid decreases in circulating Sézary cells and/or the size of mycosis fungoides tumors” after treatment with TTI-621.
Nine of the 10 patients had a reduction in CAILS score from baseline, and 3 had a reduction in circulating Sézary cells.
There were no dose-limiting toxicities, so the 10 mg dose given 3 times a week for 2 weeks was considered the optimal dose schedule.
About orphan designation
The FDA grants orphan designation to products intended to treat, diagnose, or prevent diseases/disorders that affect fewer than 200,000 people in the US.
The designation provides incentives for sponsors to develop products for rare diseases. This may include tax credits toward the cost of clinical trials, prescription drug user fee waivers, and 7 years of market exclusivity if the product is approved.
*Data in the abstract differ from the presentation.