Notice of Publication of Article on Cutaneous Angiosarcoma Phase II Study Protocol

We are pleased to announce that a paper on the protocol of the phase II investigator-initiated clinical trial of the PAI-1 inhibitor RS5614 in cutaneous angiosarcoma has been published in the scientific journal “Experimental Dermatology”.

Fujimura T, et al. Efficacy and safety of TM5614*1 in combination with paclitaxel in the treatment of paclitaxel-resistant cutaneous angiosarcoma: Phase II study protocol. Experimental Dermatology. 2023 online. (

Cutaneous angiosarcoma*2 is an extremely rare tumor of vascular endothelial cells*3. The anticancer drug paclitaxel*4 is the primary treatment for cutaneous angiosarcoma, but even with chemotherapy (paclitaxel) and radiation therapy, long-term shrinkage or disappearance of the cancer is difficult to achieve in the majority of cases. However, there is currently no standard treatment for angiosarcoma refractory to paclitaxel, and the development of a second-line treatment with high efficacy and safety is eagerly desired.

PAI-1, which is produced by vascular endothelium, is strongly expressed in angiosarcoma, and it has been reported that angiosarcoma with strong PAI-1 expression is inadequately treated with paclitaxel. Non-clinical studies strongly suggest that the combination of the PAI-1 inhibitor RS5614 and paclitaxel may enhance apoptosis*5 of angiosarcoma cells.

The phase II investigator-initiated clinical trial to evaluate the efficacy and safety of the combination of paclitaxel and RS5614 in patients with recurrent or unresectable angiosarcoma who have been previously treated with paclitaxel and are still receiving paclitaxel after paclitaxel failure (second-line treatment patients) will be conducted in collaboration with Tohoku University, Jichi Medical University, Kyushu University, Nagoya City University, National Cancer Center Hospital, Cancer Institute Hospital, and other universities/medical institutions according to the protocol in this paper. If the efficacy can be verified in this study, a new treatment method can be proposed for patients with cutaneous hemangiosarcoma for whom no effective treatment is available.

As announced on October 26, 2023, the project has enrolled its first subject and initiated the phase II study. We hope to bring this drug to patients with cutaneous angiosarcoma as soon as possible.

*1        TM5614

Clinical development number of RS5614 (PAI-1 inhibitor) .

*2        Cutaneous angiosarcoma

Angiosarcoma is a type of skin cancer. The angiosarcoma of the scalp is particularly rare (about 2.5 cases per million), but it is extremely malignant, progresses rapidly, and the disease-free survival rate at 5 years is reported to be less than 20%. No standard treatment has been established, and multiple possible treatments are immediately implemented at each medical facility.

*3        Vascular endothelial cell

These cells line the lumen of blood vessels. Vascular endothelial cells not only build blood vessels, but also play roles for exchange of substances such as oxygen and nutrients between blood and tissues. They also produce various physiologically active substances to maintain tissue and organ functions.

*4        Paclitaxel

It is a chemotherapeutic agent (anticancer drug) discovered to have anticancer activity in the bark of the Pacific yew (Taxus brevifolia), and is now chemically synthesized. It is considered to bind to “microtubules” involved in cell division, thereby stopping the division of cancer cells and causing the cell death.

*5        Apoptosis

This is a cell death phenomenon in which the cell itself commits suicide by activating its own program. Apoptosis eliminates the cells no longer needed.