Longitudinal changes in serological immune responses for NY-ESO-1 and XAGE-1.

Antibody responses in the phase Ib trial were analyzed for NY-ESO-1 (a) and XAGE-1 (b) in patients with positive antibody responses at baseline or during the KW-0761 treatment. (TIF)</p

Representative CT imaging in patients with a durable clinical response.

(a) Esophageal cancer patient B-09. Pleural metastasis (yellow arrow) was observed on CT and FDG-PET at baseline. The pleural tumor was decreased in size by the KW-0761 treatment, which was also confirmed by a reduction in standardized uptake value-max (SUV-max) on FDG-PET. Although pleural metastasis shrank, abdominal lymph node metastasis (orange arrow) developed after 23 infusions, which was evaluated as a new lesion, leading to the discontinuation of treatment. (b) Esophageal cancer patient B-39. Multiple liver metastases (yellow arrow) were observed on CT at baseline. Disease progression and a new lesion in the liver (red arrow) were confirmed after the first 8 infusions; however, all lesions subsequently decreased in size. The objective feasible response was sustained until 36 weeks after the first treatment when abdominal lymph node metastasis developed (orange arrow).</p

Blood laboratory data and clinical responses.

IntroductionRegulatory 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.MethodsForty-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.ResultsGrade 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.ConclusionsA 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.</div