E777 is a reformulation of a previous FDA approved agent for CTLC that was pulled from the market voluntarily for improvements.
Enrollment in a phase 3 trial of I/ONTAK (E7777) for the treatment of patients with persistent or recurrent cutaneous T cell lymphoma (CTLC) has been completed, according to a press release by Citius Pharmaceuticals, Inc.
I/ONTAK is a recombinant fusion protein that works through combining the interleukin-2 (IL-2) receptor binding domain with diphtheria toxin fragments. It binds IL-2 receptors on the cell surface, which causes diphtheria toxin fragment that have entered cells to inhibit protein synthesis. The agent is a reformulation of the previously FDA-approved oncology treatment ONTAK, which was marketed from 2008 to 2014. I/ONTAK was voluntarily withdrawn from the market for manufacturing improvements. The improvements made maintain the amino acid sequence but improves upon purity and bioactivity. The reformulation was granted an orphan drug designation in 2013 for the treatment of CTCL.
The phase 3, open label trial (NCT01871727) has a target enrollment of 115 participants and an estimated study completion date of December 6, 2021. The primary end points of the study are dose-limiting toxicities, maximum tolerated dose, and objective response rate.
Secondary end points include duration of response, time to response, objective response rate, the number of participants with adverse events, maximum drug concentration, area under the curve, terminal elimination half-life, time to reach maximum concentration after drug administration, total body clearance, number of participants with skin response in the main study, duration of skin response in the main study, and time to skin response in the main study.
During the single-arm study, participants will be administered the agent over 60 minutes on 5 consecutive days during every 21-day cycle.
The main part of the study enrolled 70 patients. Positive efficacy data from an initial 21-subject lead-in study found that the optimal dose level was 9 micrograms per kilogram.
In order to participate in the study, patients must be 18 years of age or older, have a confirmed diagnosis of CTCL, a history of prior therapies for CTCL, a minimum washout period of 4 weeks after previous CTCL therapy, an ECOG performance status of 0, 1, or 2, a life expectancy greater than or equal to 3 months, adequate bone marrow reserves, normal hepatic function, and adequate renal function.
Patients who have received prior denileukin diftitox therapy, the use of topical steroids within 14 days of day 1 of initial therapy, another active malignancy, serious intercurrent illness, significant pulmonary symptoms or disease, a history of uncontrolled seizures disorders, or active central nervous system disease, major surgery within 2 weeks of study enrollment, significant or uncontrolled infection, or known HIV infection are not eligible to participate.
"Completing enrollment in the Pivotal Phase 3 study of I/ONTAK moves us another step closer to expanding treatment options for patients suffering from advanced CTCL. We expect I/ONTAK's unique mechanism-of-action to offer oncologists an important therapeutic alternative to current targeted therapies which have limited duration of response and are often discontinued due to toxicity. We look forward to reviewing the complete safety and efficacy data and anticipate providing topline results in the first half of next year, followed by a biologic licence application submission in the second half of 2022," stated Myron Holubiak, chief executive officer of Citius, in a press release.