E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma: A phase I study. Issue 3 (26th February 2018)

• Record Type: Journal Article
• Authors: Ohmachi, Ken; Ando, Kiyoshi; Ogura, Michinori; Uchida, Toshiki; Tobinai, Kensei; Maruyama, Dai; Namiki, Masayuki; Nakanishi, Tadashi
• Is Part Of: Cancer science. Volume 109:Issue 3(2018)
• Page Start: 794
• Page End: 802
• Publication Date: 2018-02-26
• Subjects: cutaneous T‐cell lymphoma -- E7777 -- Japanese patients -- peripheral T‐cell lymphoma -- phase I study; Cancer -- Periodicals; Neoplasms -- Periodicals; Research -- Periodicals; Electronic journals; 616.994005
• DOI: 10.1111/cas.13513
• Languages: English
• ISSNs: 1347-9032

Abstract

Abstract : E7777, a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin‐2, shares an amino acid sequence with denileukin diftitox but has improved purity and an increased percentage of active protein monomer species. A phase I study was carried out to evaluate the tolerability, safety, pharmacokinetics, and antitumor activity of E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma. E7777 (6, 12, and expanded 9 μg/kg/day) was given to 13 patients by i.v. infusion on five consecutive days per 21‐day cycle. Dose‐limiting toxicities, including increased alanine aminotransferase, hyponatremia (n = 2), hypokalemia, lymphopenia, fatigue, hypoalbuminemia, rash, and increased lipase (n = 1), were observed in all three patients in the 12 μg/kg/day cohort, whereas two of six patients in the 9 μg/kg/day cohort showed decreased appetite or fatigue. The maximum tolerated and recommended dose of E7777 was 9 μg/kg/day for five consecutive days per 21‐day cycle. The objective response rate was 38% (5/13) and did not appear to depend on tumor expression of CD25. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful antitumor activity was observed. Subsequent studies of E7777 for T‐cell lymphomas are warranted. This study was registered withwww.ClinicalTrials.gov (NCT1401530). Abstract : E7777 is a recombinant cytotoxic fusion protein comprising diphtheria toxin fragments A and B and human interleukin‐2. A phase 1 study was conducted in Japanese patients with relapsed/refractory peripheral and cutaneous T‐cell lymphoma. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful anti‐tumour activity was observed.