Phase III trial of I/Ontak shows results in cutaneous T-cell lymphoma

The topline results for I/Ontak (denileukin diftitox), a purified and more bioactive formulation of previously marketed ONTAK, were consistent with the prior formulation. Moreover, no new safety signals were identified. Based on this data, Citius anticipates filing a biologics license application (BLA) with the FDA in the second half of 2022.

Study (E7777-G000-302) is a pivotal, multicenter, open-label, single-arm study of I/Ontak (E7777) in subjects with persistent or recurrent CTCL (NCT01871727). All subjects were diagnosed with Mycosis Fungoides or Sézary Syndrome, with tumors assessed as positive for expression of the CD25 subunit of the IL-2 receptor.

The primary outcome measure of Study 302 is the Objective Response Rate (ORR) based on the Global Response Score (GRS) (Olsen, JCO 2011). ORR is defined as the proportion of subjects with a significant reduction in tumor size that can be classified as achieving either a partial response (PR) or a complete response (CR). According to the trial protocol, the treatment would be considered efficacious and demonstrate clinical benefit if the lower limit of the 2-sided 95% exact confidence interval (CI) of the observed ORR exceeds 25.0%, as determined by the Independent Review Committee (IRC); In this study, the IRC determined the study achieved an ORR of 36.2%, 95% confidence interval (25.0%, 48.7%) (25 patients out of 69); An Investigator Efficacy Analysis determined that the study achieved an ORR of 42.3%, 95% confidence interval (30.6%, 54.6%) (30 patients out of 71).

The FDA recently provided additional written comments indicating that their efficacy evaluation will be based on study results showing the lower limit of a 95% confidence interval to exceed a clinically relevant response rate (determined during BLA review) which may be supported with data from from the prior ONTAK study that led to ONTAK's intial approval. In our trial ORR will need to be supported by adequate magnitude of duration of response and an acceptable risk/benefit ratio; Overall rates of adverse events and serious adverse events were consistent with published data of previously approved ONTAK. Most common adverse events included: nausea, fatigue, increased alanine aminotransferase, chills and peripheral oedema. No new safety concerns were identified. The study evaluated additional secondary and exploratory endpoints that include progression free survival, duration of response, time to response, skin response, duration of skin response, time to skin response, ORR (Prince, JCO 2010) and safety. These results reflect preliminary topline data and are subject to further analysis. These data as well as full detailed results will be presented at upcoming scientific conferences and submitted for publication.