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KW-0761 May Reduce Immune System–Suppressing Treg Cells in Patients With Solid Tumors

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Key Points

  • A phase Ia clinical trial of KW-0761, a humanized anti-CCR4 monoclonal antibody, in patients with lung or esophageal cancer has found that the therapy dramatically reduced the number of immune cells called Tregs in the blood of the patients and generated a possible immune response.
  • Four of the 10 patients enrolled in the study had stable disease and were long-term survivors.
  • Combined use of KW-0761 to deplete FoxP3+ Tregs with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, is a promising approach to augment immune responses.

A small phase Ia clinical trial investigating whether depleting immune cells called Tregs, which can inhibit anticancer immune responses, with KW-0761, a humanized anti-CCR4 monoclonal antibody, in patients with lung or esophageal cancer has found that the therapy dramatically reduced the number of Tregs in the blood of the patients and generated a possible immune response. Combining KW-0761 with other immunotherapies, such as cancer vaccines or checkpoint inhibitors, according to the study, is a promising approach to augmenting immune responses in patients with cancer. The study by Kurose et al is published in Clinical Cancer Research.

Study Methodology

The study was part of an investigator-initiated phase Ia/b clinical trial of KW-0761 (mogamulizumab) infusion in patients with CCR4-negative advanced or recurrent solid tumors. The researchers infused KW-0761 in seven patients with non–small cell lung cancer and three patients with esophageal cancer. The patients were recruited into the study at the Kawasaki Medical School in Kurashiki, Japan.

The primary endpoint of the dose-escalation study was the safety and pharmacokinetic profile of KW-0761 for patients with advanced or recurrent cancer. The secondary endpoints included the Treg depletion effect in peripheral blood mononuclear cells compared with the baseline, as well as the overall response rate, progression-free survival, and overall survival.

Patients received KW-0761 at 0.1 mg, 0.5 mg, or 1.0 mg weekly for 8 weeks and then monthly until disease progression. Blood samples were obtained before the first treatment and then every 4 weeks and were analyzed by flow cytometry to determine the numbers of different immune cells.

Study Findings

The study results showed that KW-0761 infusion was safe and well tolerated. No dose-limiting toxicity was observed. The number of FoxP3+CD4+ Tregs were efficiently depleted in peripheral blood mononuclear cells after the KW-0761 infusion and the effect was generally durable for more than 6 months after finishing eight infusions of the therapy. Four of the 10 patients showed stable disease during treatment and were long-term survivors.

“We were pleased to see that infusion of even a small amount of the KW-0761 efficiently depleted Tregs from the peripheral blood for a long time,” said Eliichi Nakayama, MD, PhD, Professor at Kawasaki University of Medical Welfare in Kurashiki, Japan, and a coauthor of the study, in a statement. “Unfortunately, we observed only a modest induction of antitumor immune responses and no marked clinical responses with KW-0761 monotherapy. Thus, we are planning to investigate whether combining Treg depletion with other immunotherapies, such as checkpoint inhibitors, can augment the antitumor immune response in patients with cancer.”

Dr. Nakayama is the corresponding author for the Clinical Cancer Research article.

Author disclosures of potential conflicts of interest can be found at the end of the study abstract at clincancerres.aacrjournals.org. The study was funded by the Ministry of Health, Labour, and Welfare, Japan; the Ministry of Education, Culture, Sports, Science and Technology of Japan; and by the Japan Society for the Promotion of Science.

 

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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