This study evaluated whether adding E7777 (a new formulation of denileukin diftitox [DD]) improved the efficacy of anti-PD-1 antibody therapy. Treatment with E7777 was safe and well-tolerated. Combined E7777 and anti-PD-1 therapy was well tolerated and more effective than monotherapy with either drug.
No new safety signals were observed with E7777 when compared to the safety profile of ONTAK. There is no evidence of cumulative toxicity. Most patients had at least 1 TEAE which were mostly Grade 1/2.
Approximately half (34 of 69; 49.3%) of patients had prior exposure to 1 or more FDA-approved targeted therapeutics: romidepsin, brentuximab, or mogamulizumab. In study 302, E7777 at a dose of 9 mcg/kg/day demonstrated clinical efficacy and clinically meaningful benefit in heavily pre-treated patients with relapsed/refractory CTCL. The ORR of 36.2% per IRC (42.3% by investigator assessment) showed that a substantial proportion of these heavily pretreated patients experienced clinical benefit after E7777 treatment similar to ONTAK. The observed tumor responses were rapid, durable, and deep.
Therefore, safety monitoring activities have been continued along with alerting related events. Based on these results, E7777 obtained a new drug approval in Japan in March 2021 for the indication of relapsed or refractory PTCL/CTCL.