STCube Confirms Competitiveness of BTN1A1-Targeted Immunotherapy Strategy

STCube presented a roadmap for next-generation non-small cell lung cancer (NSCLC) treatment strategies at the World Conference on Lung Cancer (WCLC 2025).

On September 15, STCube announced its plans to identify patients using the expression of the novel immuno-oncology target BTN1A1, and to advance its BTN1A1-targeted immunotherapy, Nelmastobat, into Phase 2 clinical trials for NSCLC. The company also revealed its intention to release these plans.

STCube is preparing a Phase 2 clinical trial combining Nelmastobat with docetaxel in patients with BTN1A1-positive advanced or metastatic NSCLC. On August 26, the company submitted the Phase 2 investigational new drug (IND) application to the Ministry of Food and Drug Safety.

In preclinical studies using patient-derived NSCLC organoids (PDOs), the combination of Nelmastobat and docetaxel demonstrated the strongest tumor suppression effect compared to docetaxel monotherapy or combination with PD-1/PD-L1 inhibitors. Docetaxel upregulated BTN1A1 expression, thereby increasing responsiveness to Nelmastobat. This effect was particularly pronounced in the PD-L1-negative patient group.

Yoo Seunghan, Chief Scientific Officer at STCube, stated, "BTN1A1 is highly expressed in chemotherapy-resistant cancer cells, and its expression further increases when combined with chemotherapeutic agents, thereby enhancing the antitumor efficacy of Nelmastobat." He added, "The combination of Nelmastobat and docetaxel is expected to become a promising treatment strategy for PD-L1-negative and immunotherapy-refractory NSCLC patients."

NSCLC accounts for approximately 80-85% of all lung cancers and is the most common type. Docetaxel is mainly used as second-line chemotherapy for patients with advanced or recurrent NSCLC. Due to limited survival benefits and side effects, there is significant unmet need for new treatment options. BTN1A1-positive expression has been confirmed in about 50% of patients, indicating that a broad patient population could potentially benefit clinically from Nelmastobat.

The STCube research team conducted multiplex immunofluorescence analysis using NSCLC tumor tissue microarrays. As a result, BTN1A1 expression was observed in about half of all patients and showed a negative correlation with PD-L1 expression. Notably, tissues with high BTN1A1 expression also exhibited increased nuclear YAP1 expression, and the co-expression of YAP1 was found to enhance predictive power.

Yoo further explained, "BTN1A1 tends to be co-expressed with nuclear YAP1, which is associated with chemotherapy resistance, as well as being expressed independently. We are continuing to study the interactions between BTN1A1 and other cancer-related proteins."

BTN1A1 is a novel immune checkpoint protein expressed in both tumor cells and immune cells, mainly observed in dormant or slow-growing cancer cells. It exhibits a mutually exclusive expression pattern with PD-L1 and is reported to have high expression rates in major solid tumors, including NSCLC and colorectal cancer. It is gaining attention as a new therapeutic alternative for patients who are unresponsive or have developed resistance to standard treatments.