E777 Shows Encouraging Safety in Cutaneous T-Cell Lymphoma

Data from the phase 3 trial of I/ONTAK (E7777, NCT01871727), an engineered IL-2-diphtheria toxin fusion protein, were consistent with the prior formulation of the agent and no new safety signals were identified when administered to patients with persistent or recurrent cutaneous T-cell lymphoma (CTCL), according to a press release Citius Pharmaceuticals, Inc. (Citius).¹

Based on this data, a biologics license application (BLA) is expected to be filled by Citius to the FDA in the second half of 2022.

"We are encouraged by the results of the study, which we believe are clinically meaningful, and are hopeful that I/ONTAK will be an important treatment option for patients with persistent or recurrent CTCL. There is no single standard of care for this orphan disease. We believe the full body of data from this, and prior studies will support a successful reintroduction of denileukin diftitox to the market. We are eager to move forward with a BLA submission for the treatment of CTCL later this year. This important milestone brings Citius one step closer to launching its first commercial product next year, if approved by the FDA," stated Myron Holubiak, chief executive officer of Citius, in the press release.

The multicenter, open-label, single-arm study of E7777, examines the engineered IL-2-diphtheria toxin fusion protein in patients with persistent or recurrent CTCL.² The study was conducted in 2 parts consisting of an initial lead-in part which aimed to select the recommended dose of E7777, followed by the main part which aimed to test efficacy.

The trial completed enrollment in December 2021, with a total of 112 patients. Eligibility was open to participants aged 18 and older with a histopathologic diagnosis of CTCL. Patients were also required to have CD25 assay-positive tumor, an ECOG performance stats of 0-2, life expectancy of 3 months or more, and adequate bone marrow reserves.

Additionally, CTCL disease stage at study entry was stage IA - IV, except participants with CNS involvement, in the lead-in part and stage I - III in the main study.

The lead-in study included 21 subjects treated at doses of 6 to 15 µg/kg/day, while 91 subjects with stage I-IV CTCL were enrolled in the main study where they were administered 9 μg/kg/day of I/ONTAK (E7777) by intravenous infusion over 60 minutes on 5 consecutive days per cycle every 21 days.

Primary end points of the trial include dose-limiting toxicities and maximum tolerated dose in the lead-in part, and overall response rate (ORR) in the main study. Some secondary end points between both studies consist of duration of response, time to response, number of participants with adverse events (AEs), and maximum drug concentration.

Of the patients enrolled, a total of 71 with Stage I-III persistent or recurrent CTCL from the lead-In and main studies were assessed for efficacy with 69 subjects included in the primary efficacy analysis set.

Findings revealed an ORR of 36.2%, (95% CI, 25.0%-48.7%) was demonstrated in a total of 25 patients out of the 69. An investigator efficacy analysis also found the study to achieve an ORR of 42.3% in 30 of the 71 patients (95% CI, 30.6%-54.6%).

The rates of both AEs and serious AEs stayed consistent with previously reported data. Some of the most common AEs included nausea, fatigue, increased alanine aminotransferase, chills and peripheral oedema. Additionally, no new safety concerns were identified.

Based on the positive results which reflect preliminary topline data, further analysis is to be expected while detailed results will also be presented at upcoming scientific conferences and submitted for publication.

​​"The topline results demonstrated anti-tumor activity in the treatment of persistent or recurrent CTCL, an incurable disease. Based on the topline data, I/ONTAK provided disease control without cumulative toxicity. I/ONTAK has a unique dual mechanism of action that exerts both direct tumor cell killing and transient elimination of immunosuppressive Tregs within the tumor microenvironment. The topline data further demonstrate that I/ONTAK has an average time to response within one to two cycles of treatment in patients that have failed multiple prior therapies. If approved, we believe this biologic with its observed efficacy and safety data, and which is already approved for CTCL and peripheral T-cell lymphoma patients in Japan, would arm oncologists in the United States. with an important additional treatment option for this devastating orphan disease," added Myron Czuczman, MD, chief medical officer of Citius, in the press release.

REFERENCES:

1. Citius pharmaceuticals reports topline data from the pivotal phase 3 study of cancer immunotherapy I/ONTAK (E7777) for the treatment of persistent or recurrent cutaneous T-Cell lymphoma (CTCL) in support of BLA submission. Citius Pharmaceuticals, Inc. April 6, 2022. Accessed April 6, 2022. https://prn.to/37pED7P

2. A trial of E7777 in persistent and recurrent cutaneous T-Cell lymphoma. ClinicalTrials.gov. Accessed April 6, 2022. https://bit.ly/3uYT8r9