Integrated Analysis of Phase 1a and 1b Randomized Controlled Trials; Treg-targeted Cancer Immunotherapy with the Humanized Anti-CCR4 Antibody, KW-0761, for Advanced Solid Tumors

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2023 Sep 20

PMID 37729184

Authors

Kaoru Fujikawa

Takuro Saito

Koji Kurose

Takashi Kojima

Takeru Funakoshi

Eiichi Sato

Kazuhiro Kakimi

Shinsuke Iida

Yuichiro Doki

Mikio Oka

Ryuzo Ueda

Hisashi Wada

Affiliations

Soon will be listed here.

Abstract

Introduction: Regulatory T cells (Tregs) have attracted attention as a novel therapeutic target to augment the clinical efficacy of immunotherapy. We conducted phase Ia and Ib trials to examine the safety and efficacy of the anti-CCR4 antibody, KW-0761 (mogamulizumab), which may eliminate effector Tregs (eTregs). We herein overviewed the results of these trials, presented cases with a durable clinical response, and investigated factors associated with the clinical effects of KW-0761.

Methods: Forty-nine patients with CCR4-negative solid cancers were enrolled in the phase Ia and Ib trials on KW-0761. An integral analysis of safety, clinical responses, prognosis, blood laboratory data, and cancer testis antigen-specific immune responses was performed.

Results: Grade 3-4 treatment-related adverse events were reported in 21 (42.9%) out of 49 patients, all of which were manageable. A partial response and stable disease were observed in 1 and 9 patients, respectively. A durable clinical response was noted in 2 esophageal and 2 lung cancer patients. eTreg depletion in peripheral blood was confirmed in most patients, and eTreg depletion was sustained during the KW-0761 treatment. High lymphocyte levels at baseline and 2 weeks after the initiation of KW-0761 were associated with a favorable clinical outcome.

Conclusions: A durable clinical response was noted in some patients, and high lymphocyte levels before treatment initiation may be a biomarker for the efficacy of KW-0761. The synergistic effect of KW-0761 for depleting Tregs and other immunotherapies is expected in the future.

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