E7777 in Japanese patients with relapsed/refractory peripheral and cutaneous T-cell lymphoma: A phase 1 study

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 1 study was conducted to evaluate the tolerability, safety, pharmacokinetics and anti-tumour 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 administered to 13 patients via intravenous infusion on 5 consecutive days per 21-day cycle. Dose-limiting toxicities, including alanine aminotransferase increased, hyponatraemia (n = 2), hypokalaemia, lymphopenia, fatigue, hypoalbuminaemia, rash and lipase increased (n = 1), were observed in all 3 patients in the 12 μg/kg/day cohort, whereas 2 of 6 patients in the 9 μg/kg/day cohort exhibited decreased appetite or fatigue. The maximum tolerated and recommended dose of E7777 was 9 μg/kg/day for 5 consecutive days per 21-day cycle. The objective response rate was 38% (5/13) and did not appear to depend on the tumour expression of CD25. E7777 was well tolerated, assuming careful management of adverse events during treatment, and preliminary but clinically meaningful anti-tumour activity was observed. Subsequent studies of E7777 for T-cell lymphomas are warranted. This study was registered with www.ClinicalTrials. gov (NCT1401530).

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