A phase II multicentre study of plasminogen activator inhibitor-1 inhibitor (TM5614) plus nivolumab for treating anti-programmed cell death 1 antibody-refractory malignant melanoma
TM5614-MM trial
- Fujimura, Taku Conceptualization; Data curation; Formal analysis; Funding acquisition; Investigation; Project administration; Resources; Writing - original draft
- Yoshino, Koji Resources; Writing - review & editing
- Kato, Hiroshi Resources; Writing - review & editing
- Fukushima, Satoshi Resources; Writing - review & editing
- Ishizuki, Shoichiro Resources
- Otsuka, Atsushi Resources
- Matsushita, Shigeto Conceptualization; Resources; Writing - review & editing
- Amagai, Ryo Resources
- Muto, Yusuke Resources
- Yamazaki, Emi Resources
- Kambayashi, Yumi Resources
- Yahata, Takashi Conceptualization; Investigation; Supervision
- Miyata, Toshio Conceptualization; Investigation; Project administration; Supervision
- Fujisawa, Yasuhiro Conceptualization; Methodology; Project administration; Resources; Writing - review & editing
- Asano, Yoshihide Supervision; Writing - review & editing
Lay Summary
Types of antibody called ‘anti-programmed cell death 1 antibodies’ (also known as ‘anti-PD-1 Abs’) are commonly used to treat a range of different advanced cancers, including melanoma. However, less is known about the effectiveness of anti-PD-1 Abs, especially in Asian populations. There remains an unmet need to improve anti-PD-1 Ab-treatment, particularly in people with melanoma who are ‘refractory’ (or do not respond) to anti-PD-1 Abs in Japan.
To evaluate anti-PD-1 Ab-treatment, we carried out a clinical trial called the ‘TM5614-MM study’ to investigate the safety and efficacy of using a combination of drugs (TM5614 and nivolumab). People with advanced and ‘unresectable’ (cannot be surgically removed) malignant melanoma were recruited from seven Japanese institutes between 13 September 2021 and 31 March 2023. Those with metastatic or unresectable melanoma who had received prior treatment with or without anti-PD-1 Abs were enrolled. The main result that we measured was the response rate after 8 weeks of treatment with TM5614.
We found that the response rate at 8 weeks was 25.9% in 27 patients who were anti-PD-1-Ab-refractory (those who had received prior treatment with anti-PD-1 Abs) and 0% in four patients in the anti-PD-1 Ab-naïve group (those who had not previously received treatment with anti-PD-1 Abs). Treatment-related severe adverse events occurred in three of 39 patients (7.7%).
Overall, our study findings suggest that TM5614 in combination with nivolumab is well tolerated and could be effective in anti-PD-1 Ab-refractory unresectable melanoma.