Phase I, multicenter, dose-escalation study of avadomide in adult Japanese patients with advanced malignancies.

Autor: Hatake K; Lymphoma/Hematology Center, International University of Health and Welfare, Mita Hospital, Tokyo, Japan., Chou T; Department of Hematology Oncology, Niigata Cancer Center Hospital, Niigata, Japan., Doi T; Department of Experimental Therapeutics, National Cancer Center Hospital East, Chiba, Japan., Terui Y; Department of Hematology Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Tokyo, Japan., Kato H; Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan., Hirose T; Department of Hematology Oncology, Niigata Cancer Center Hospital, Niigata, Japan., Seo S; Department of Hematology and Oncology, Dokkyo Medical University, Tochigi, Japan., Pourdehnad M; Bristol Myers Squibb, Princeton, NJ, USA., Ogaki Y; Celgene K.K., A Bristol Myers Squibb Company, Tokyo, Japan., Fujimoto H; Celgene K.K., A Bristol Myers Squibb Company, Tokyo, Japan., Hagner PR; Bristol Myers Squibb, Princeton, NJ, USA., Yamamoto K; Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
Jazyk: angličtina
Zdroj: Cancer science [Cancer Sci] 2021 Jan; Vol. 112 (1), pp. 331-338. Date of Electronic Publication: 2020 Nov 26.
DOI: 10.1111/cas.14704
Abstrakt: Non-Hodgkin lymphoma (NHL) treated with chemoimmunotherapy has limited efficacy in some patients, resulting in relapsed or refractory disease. Avadomide (CC-122) is a novel cereblon-binding agent that exhibits antilymphoma and immune-modulation activities with a biological profile distinct from similar agents, such as lenalidomide. This phase I multicenter study evaluated avadomide in Japanese patients with advanced solid tumors or NHL. Fourteen patients with NHL and one with a solid tumor (esophageal carcinoma), were enrolled in four dose-escalation cohorts using a 3 + 3 design. Primary endpoints included safety, dose-limiting toxicities (DLT), maximum-tolerated dose and/or recommended phase II dose (RP2D), and pharmacokinetics. Secondary endpoints included overall response rate (ORR) and duration of response. One patient with NHL experienced DLT, which included face edema, pharyngeal edema, and tumor flare (all grade 1) that led to a dose reduction. Eleven patients had grade ≥3 treatment-emergent adverse events, most frequently decreased neutrophil count (33%) and decreased lymphocyte count (20%). The ORR in patients with NHL (n = 13) was 54%, including four complete and three partial responses. The best response for the solid tumor patient was progressive disease. Avadomide dose intensity was consistent across cohorts, and the 3-mg dose given five consecutive days/week was established as the RP2D. This phase I study identified a tolerable dose of avadomide, with an acceptable toxicity profile and clinically meaningful efficacy in Japanese patients with previously treated NHL.
(© 2020 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)
Databáze: MEDLINE
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