Notice of a newspaper article publication regarding the start of Phase III clinical trial for malignant melanoma with a PAI-1 inhibitor RS5614

A Phase III clinical trial for the PAI-1 (plasminogen activator inhibitor 1) inhibitor RS5614, which is given orally to enhance the therapeutic effect in malignant melanoma for which immune checkpoint inhibitors are ineffective, have begun at Tohoku University. RS5614 is a Japanese drug developed in collaboration with academia including Tohoku University, from discovery to optimization, nonclinical GLP testing, GMP synthesis and formulation, and Phase I to Phase III trials. A press release was issued on this matter at Tohoku University’s headquarters, medical school, and university hospital on February 19, and a newspaper article was published in Nikkei Biotech on February 18, Kahoku Shimpo on February 20, and February 21 issue of the Science Newspaper.

• The incidence rate of malignant melanoma patients is low at 1.5 to 2 per 100,000 in Japan, and the total number of patients in Japan is about 5,000, making it a rare disease. However, in the United States, it is a common skin cancer with 21 per 100,000, and the number of patients is about 1.41 million.

• With the advent of immune checkpoint inhibitors such as the anti-PD-1 antibody nivolumab, the treatment of malignant melanoma has improved significantly and, furthermore, the anti-CTLA-4 antibody ipilimumab has been developed, so combination therapy to increase the response rate of anti-PD-1 antibodies alone is being implemented. However, due to serious side effects on the immune system, the incidence of treatment discontinuation is four times higher than with monotherapy, and this combination therapy also leads to high medical costs, so the development of a safe oral medication that has little side effects and increases the response rate is eagerly awaited.

• In a phase II clinical trial with RS5614, the response rate only at 8 weeks after treatment in 27 patients was 25.9% (7 cases, 1 complete response, 6 partial responses), and the disease control rate, including stable disease, was 66.7% (PPS evaluation). In addition, the primary endpoint of response rate at 8 weeks of combination therapy, 25.9%, was an excellent result that exceeded the historical control response rate of 13.5% in Japan for the combination of nivolumab and ipilimumab, which is already approved as a treatment. Of particular note, despite the short combination period of only 2 months, the result was significantly higher than the response rate of nivolumab plus ipilimumab combination therapy as a second-line treatment. Furthermore, of the 7 cases of serious adverse events that occurred in nivolumab ineffective cases, only 2 cases of liver dysfunction were likely to be causally related to the investigational drug, demonstrating that the combination of nivolumab plus RS5614 is safer than the combination of nivolumab + ipilimumab.

This Phase 3 study is a randomized, placebo-controlled, double-blind clinical trial to evaluate the efficacy and safety of RS5614 in combination with nivolumab in 124 patients with unresectable melanoma, and will be conducted at 18 institutions across Japan, including Tohoku University Hospital (Tohoku University Hospital, Sapporo Medical University Hospital, Hirosaki University Hospital, Jichi Medical University Saitama Medical Center, National Cancer Center Hospital East, National Cancer Center Hospital, Cancer Institute Hospital of Japanese Foundation for Cancer Research, Niigata Cancer Center Hospital, Shizuoka Cancer Center, Nagoya City University Hospital, University of Tsukuba Hospital, Gifu University Hospital, Shimane University Hospital, Ehime University Hospital, Kyushu University Hospital, Kyushu Cancer Center, Kumamoto University Hospital, and Kagoshima Medical Center).

The Science Newspaper
https://sci-news.co.jp/topics/9912/

Tohoku University
https://web.tohoku.ac.jp/research/

Tohoku University School of Medicine
https://www.med.tohoku.ac.jp/5899/

Tohoku University Hospital
https://www.hosp.tohoku.ac.jp/release/news/43570.html

The Kahoku Shimpo
https://kahoku.news/articles/20250219khn000070.html

Nikkei Biotechnology
https://bio.nikkeibp.co.jp/atcl/release/25/02/18/23308/