Announcement of Presentation on the Overview of an Investigator-Initiated Trial of PAI-1 Inhibitor RS5614 for Locally Advanced Non-Small Cell Lung Cancer at the World Conference on Lung Cancer (WCLC)

We are pleased to announce that the trial design of an investigator-initiated trial of our PAI-1 inhibitor RS5614 in locally advanced non-small cell lung cancer (NSCLC)¹⁾ was presented on September 13, 2026, by Dr. Masuda of Hiroshima University Hospital at the 2026 World Conference on Lung Cancer (WCLC), held in Seoul, South Korea.

The current standard first-line treatment for locally advanced (unresectable Stage III) NSCLC is chemoradiotherapy (CRT)²⁾ followed by one year of durvalumab³⁾ consolidation therapy⁴⁾. However, this regimen results in a 5-year progression-free survival (PFS) rate of only 33.1% and a 5-year overall survival (OS) rate of only 42.9% (N Engl J Med 2017;377:1919-29; J Clin Oncol 2022;40:1301-11), and many patients are not cured. In addition, only about 80% of patients are able to transition from initial CRT to durvalumab consolidation therapy, owing to factors such as disease progression during CRT or radiation-induced lung injury, meaning that a certain proportion of patients are unable to reach immune checkpoint inhibitor (ICI)⁵⁾ therapy — a continuing challenge in this treatment setting.

We have previously shown that cancer cells that acquire treatment resistance following chemotherapy, immunotherapy, or radiotherapy upregulate PAI-1, and that PAI-1 functions as a hub molecule supporting the survival of resistant cells through evasion of apoptosis, epithelial–mesenchymal transition, and remodeling of the tumor microenvironment (Biomed J. 2026 Feb;49(1):100911). We have also confirmed, in a mouse lung cancer model, that residual cancer cells surviving radiation exposure upregulate PAI-1 and thereby acquire radioresistance, and that PAI-1 is also involved in resistance to chemotherapeutic agents; in preclinical models, combination with RS5614 reverses these forms of resistance and enhances the antitumor effects of radiotherapy and anti-PD-1 antibody therapy (Mol Cancer Ther 2026;25:435-447). Furthermore, PAI-1 is also implicated in radiation-induced pulmonary fibrosis — lung fibrosis following radiation exposure is suppressed in PAI-1 knockout mice — and a Phase II trial of RS5614 in COVID-19 pneumonia suggested that it may suppress the worsening of lung injury (Sci Rep 2024;14:165; Exp Ther Med 2018;16:3070-6). Based on these findings, we believe RS5614 has the potential to both enhance antitumor efficacy and suppress treatment-related lung injury.

We have conducted an investigator-initiated Phase II trial across six institutions evaluating the efficacy and safety of RS5614 in combination with nivolumab in previously treated NSCLC patients (third-line or later) with multiple prior lines of chemotherapy, and disclosed the results of this trial on March 5, 2026. That trial confirmed that combination with RS5614 enhanced the antitumor effect of the immune checkpoint inhibitor, with greater efficacy observed in patients at an earlier treatment stage. Based on these findings, the trial presented on this occasion is an investigator-initiated Phase II trial designed to evaluate RS5614 in combination with chemoradiotherapy and durvalumab consolidation therapy — the first-line standard of care — in patients with locally advanced NSCLC in the first-line treatment setting, and is being conducted at 12 institutions in Japan, led by the coordinating institution, Hiroshima University Hospital. This trial was selected under the Japan Agency for Medical Research and Development (AMED)’s FY2026 (Reiwa 8) “Clinical Research and Trial Promotion Project” (disclosed March 9, 2026), and dosing of the first patient commenced on July 16, 2026 (disclosed on July 17, 2026).

This presentation provides scientific rationale for a new treatment strategy using RS5614 in locally advanced NSCLC, and proposes that combining RS5614 with the first-line standard of care — chemoradiotherapy followed by durvalumab consolidation therapy — may offer a new treatment approach that both enhances antitumor efficacy and reduces treatment-related lung injury.

1) Locally advanced non-small cell lung cancer (NSCLC): Lung cancer that has spread locally to an extent that makes surgical resection difficult.

2) Chemoradiotherapy (CRT): A first-line standard treatment used when surgery is not feasible, combining drugs that attack cancer cells (chemotherapy) with radiation directed at the tumor site (radiotherapy).

3) Durvalumab: An immune checkpoint inhibitor that binds to PD-L1 to enhance the attacking capability of immune cells; it is used primarily in NSCLC, particularly as consolidation therapy following definitive chemoradiotherapy.

4) Consolidation therapy: Additional treatment given after initial therapy (e.g., chemoradiotherapy) has brought the cancer under a degree of control, intended to maintain and strengthen the treatment effect.

5) Immune checkpoint inhibitor (ICI): An antibody therapeutic that targets immune checkpoint molecules, which normally suppress excessive immune responses against self. Cancer cells exploit these molecules to evade attack by the immune system.