Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma

Our plain-English summary of Phase 2 Study of YS110, a Recombinant Humanized Anti-CD26 Monoclonal Antibody, in Japanese Patients With Advanced Malignant Pleural Mesothelioma, by K. Nakagawa, T. Kijima, M. Okada, et al (JTO Clinical and Research Reports, 2021).

The study

• Authors: K. Nakagawa, T. Kijima, M. Okada, M. Morise, M. Kato, K. Hirano, N. Fujimoto, M. Takenoyama, H. Yokouchi, Y. Ohe, T. Hida, K. Aoe, T. Kishimoto, M. Hirokawa, H. Matsuki, Y. Kaneko, T. Yamada, C. Morimoto, M. Takeda
• Journal: JTO Clinical and Research Reports
• Published: 2021;2(6):100178
• Cited by: 11 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Introduction: YS110, a humanized monoclonal antibody with a high affinity to CD26, exhibited promising antitumor activity and was generally well-tolerated in the phase 1 part of a phase 1 and 2 Japanese trial in patients with malignant pleural mesothelioma (MPM). Here we report the results of the phase 2 part of the study.

Methods: The patients included were aged 20 years and older, had histologically confirmed MPM, were refractory to or intolerant of existing antineoplastic agents, and were not candidates for standard therapy. YS110 6 mg/kg, determined in the phase 1 dose-determination part, was given in 6-weekly cycles (5 × once-weekly infusions, followed by a 1-wk rest).

Results: The study included 31 patients (median age = 68 y, 90.3% men); 64.5% had stage IV MPM, 90.3% had greater than or equal to 20% CD26 expression in tumor tissue, and 38.7% (12 patients) had previously received nivolumab. The 6-month disease control rate was 3.2%. The best overall response was partial response in one patient and stable disease in 14 patients. The median progression-free survival was 2.8 months (both in patients who had and had not previously received nivolumab-groups A and B, respectively). Respective progression-free survival rates at 6 months were 9.1% and 31.6% in groups A and B. The median overall survival was 9.7 months. A total of 30 patients (96.8%) had at least one adverse event. Common treatment-related adverse events were infusion-related reaction (16.1%), hiccups (9.7%), and interstitial lung disease (9.7%). There were no treatment-related deaths.

Conclusions: The 6-month disease control rate did not exceed the predefined threshold, but YS110 revealed modest efficacy in response rate as salvage therapy in difficult-to-treat patients with MPM. YS110 was generally well tolerated.

© 2021 The Authors.

In plain English

This was the phase II part of an open-label, multicenter Japanese trial of YS110, an antibody against CD26. It enrolled patients with advanced malignant pleural mesothelioma who were refractory to or intolerant of existing cancer drugs and not suitable for standard therapy. Of 38 consenting patients at 12 institutions, 31 received YS110, 6 mg/kg weekly for five weeks then a week's rest, in repeated cycles. All had prior platinum-based chemotherapy; 12 had prior nivolumab. The main measure, disease control at six months, was 3.2% (1 of 31), which did not exceed the preset threshold of 23%. Best responses at any point were partial response in one patient and stable disease in 14. Median progression-free survival was 2.8 months (95% confidence interval 1.5 to 4.2); median overall survival was 9.7 months (6.9 to not reached). Thirty patients (96.8%) had at least one adverse event; in 16 (51.6%) events were judged related to YS110, including interstitial lung disease in three. There were no treatment-related deaths. The authors concluded that YS110 showed modest efficacy in response rate and was generally well tolerated.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Phase II part of a multicenter, open-label, single-arm phase I/II drug trial
• Who was studied: Japanese patients aged 20 or older with histologically confirmed malignant pleural mesothelioma that was refractory to or intolerant of existing anticancer drugs, and who were not suitable candidates for standard therapy. 38 patients from 12 institutions consented between June 2018 and March 2019, and 31 received at least one dose (median age 68; 28 men; 26 epithelioid, 3 biphasic, 2 sarcomatoid). All had prior platinum-based chemotherapy and 12 had prior nivolumab.
• Exposure: Treatment with YS110 (a humanized anti-CD26 monoclonal antibody) at 6 mg/kg, given as once-weekly infusions for 5 weeks followed by a 1-week rest, repeated in 6-week cycles. The article does not discuss asbestos exposure.
• Main results:
  • The 6-month disease control rate (all 31 patients) was 3.2% (1 of 31)
  • The 6-month disease control rate did not exceed the pre-defined threshold of 23%
  • Best overall response among the 31 patients: partial response in 1, stable disease in 14, progressive disease in 14, and not evaluable in 2
  • Disease control rate (based on best overall response) 48.4% and overall response rate 3.2% (all 31 patients)
  • Median progression-free survival in the total cohort (n = 31) was 2.8 months (95% CI 1.5 to 4.2)
  • Median overall survival in the total cohort was 9.7 months (95% CI 6.9 to not reached)
  • Median progression-free survival was 2.8 months both in patients previously treated with nivolumab (group A, 95% CI 1.4 to 5.5) and in those not previously treated with it (group B, 95% CI 1.4 to 6.9)
  • 6-month progression-free survival rates were 9.1% (95% CI 0.5 to 33.3) in group A and 31.6% (95% CI 12.9 to 52.2) in group B
  • Overall response rate and disease control rate were 8.3% and 58.3% in group A (prior nivolumab), and 0% and 42.1% in group B
  • The article reports correlation coefficients (R2) between CD26 expression and tumor shrinkage of 0.075, and between CD26 expression and progression-free survival of 0.0002
  • 30 of 31 patients (96.8%) had at least one adverse event; in 16 (51.6%) the events were related to YS110
  • The most common treatment-related adverse events were infusion-related reaction (16.1%) and hiccups (9.7%)
  • Other common treatment-related adverse events were interstitial lung disease (9.7%), diarrhea (6.5%) and pruritus (6.5%)
  • Treatment-related adverse events of grade 3 or higher occurred in 4 patients. Six serious adverse events occurred, including 2 cases of interstitial lung disease.
  • There were no treatment-related deaths
• The authors' conclusion: The authors concluded that the 6-month disease control rate did not exceed the pre-defined threshold. They said YS110 showed modest efficacy in response rate and a potential disease-stabilizing activity in this difficult-to-treat population, and was generally well tolerated. They called for further studies.
• Limitations the authors state:
  • Some patients classed as progressive disease had stable disease after the first cycle but did not meet the required time interval, so the disease control rate may be underestimated
  • The link between CD26 expression and YS110 efficacy remained unknown; the authors suggested current immunohistochemistry may not measure CD26 in tumor cells correctly
  • Survival results are affected by earlier lines of therapy and by treatments patients received after the study
  • YS110 has been given to only a small number of patients, so its relationship with interstitial lung disease is not yet clear

Topics

Medical terms in this study, explained in our Lexicon: Monoclonal Antibody, Pleural Mesothelioma, Nivolumab (Opdivo), Progression-Free Survival, Median Overall Survival, Interstitial Lung Disease.

Related studies

• Phase I study of YS110, a recombinant humanized monoclonal antibody to CD26, in Japanese patients with advanced malignant pleural mesothelioma — M. Takeda, Y. Ohe, et al. (2019)
• Phase I study of amatuximab, a novel monoclonal antibody to mesothelin, in Japanese patients with advanced solid tumors — Y. Fujisaka, T. Kurata, et al. (2015)
• A first-in-Asian phase 1 study to evaluate safety, pharmacokinetics and clinical activity of VS-6063, a focal adhesion kinase (FAK) inhibitor in Japanese patients with advanced solid tumors — T. Shimizu, K. Fukuoka, et al. (2016)
• Inhibition of mesothelin-CA-125 interaction in patients with mesothelioma by the anti-mesothelin monoclonal antibody MORAb-009: Implications for cancer therapy — R. Hassan, C. Schweizer, et al. (2010)
• Population pharmacokinetics and exposure-response relationship of amatuximab, an anti-mesothelin monoclonal antibody, in patients with malignant pleural mesothelioma and its application in dose selection — A. Gupta, Z. Hussein, et al. (2016)
• Antitumor activity of anti-C-ERC/mesothelin monoclonal antibody in vivo — K. Inami, M. Abe, et al. (2010)

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