nelmastobart (STT-003) / STCube Pharma - LARVOL DELTA

STCube reports 2 PRs and 4 SDs with nelmastobart in Phase 1b colorectal cancer trial [Google translation] (BioNews) - "These patient groups demonstrated a positive correlation between BTN1A1 expression and treatment responsiveness. In addition, immunofluorescence analysis showed that the median proportion of nuclear YAP1-expressing tumor cells among BTN1A1-positive cells was 49.89%. Clinical benefit was found to be particularly high in patients who were positive for both biomarkers....'Based on this, we are developing a refined predictive model and are optimizing our 2 clinical trial development strategy, thereby further strengthening the development potential of nelmastobart.'"

P1 data • Trial status • Colorectal Cancer

BTN1A1 expression as a biomarker for patient selection: Phase 1b IHC analysis and clinical outcomes supporting a biomarker-guided phase 2 trial in colorectal cancer. (ASCO-GI 2026) - P1/2 | "Background: Metastatic colorectal cancer (CRC) has poor prognosis in patients resistant or intolerant to oxaliplatin- and irinotecan-based chemotherapy, and durable responses to salvage regimens such as trifluridine/tipiracil plus bevacizumab remain limited...Nelmastobart, a first-in-class anti-BTN1A1 monoclonal antibody, is being tested in the STCUBE-003 Phase Ib/II trial (NCT06873763) in combination with trifluridine/tipiracil and bevacizumab... BTN1A1 was consistently expressed across all tumors, with high TPS associated with favorable outcomes. These findings support BTN1A1 as a robust biomarker for patient selection and provide rationale for the ongoing BTN1A1-guided Phase 2 trial."

Biomarker • Clinical • Clinical data • IO biomarker • P1 data • P2 data • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Solid Tumor • BTN1A1 • CD8 • PD-L1 • SLFN11 • YAP1

Nelmastobart in Combination With Docetaxel in Non Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: STCube, Inc.

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Professor Lee Soo-hyun and her research team from the Department of Oncology at Korea University Anam Hospital presented findings from the Phase 1b and Phase 2 trials evaluating the combination therapy of Nelmastobart + capecitabine. [Google translation] (BioNews) - "Among them, 30 patients (57.7%) had liver metastases, 42 (80.8%) had microsatellite-stable (MSS) colorectal cancer, and 23 (44.2%) carried genetic mutations (RAS or BRAF). In the Phase 2b trial, no DLTs associated with nelmastobart were reported, and the RP2D was confirmed as nelmastobart 800 mg and capecitabine 1000 mg/m2....The efficacy analysis (data cutoff date: June 13, 2025) revealed that 7 out of the 52 enrolled patients achieved a partial response (PR), while 33 exhibited stable disease (SD), resulting in an objective response rate (ORR) of 13.5% (7/52) and a disease control rate (DCR) of 77.0% (40/52). The median progression-free survival (mPFS) was 4.2 months, indicating superior therapeutic efficacy compared with the standard of care (ORR 0-6%, mPFS 2-3 months)....As several patients remain on treatment, the final analysis, including overall survival (OS), has been rescheduled for release in H1 2026."

P1/2 data • Colorectal Cancer

STCube's Phase 1b clinical trial in colorectal cancer demonstrates tumor reduction in all patients, highlighting strong efficacy and tolerability [Google translation] (BioNews) - "The Phase 1b safety evaluation revealed no dose-limiting toxicities (DLTs). The most frequently observed adverse events were leukopenia and neutropenia, both associated with chemotherapy rather than with Nelmastobart itself. Based on these findings, the recommended RP2D was established as Nelmastobart 800 mg, TAS-102 35 mg/m2, and bevacizumab 5 mg/kg....According to the company, based on the predefined efficacy criteria (BTN1A1 TPS ≥ 50), the objective response rate (ORR) was 40% (2/5), and the disease control rate (DCR) reached 100% (5/5), indicating that the initial data exceeded the current standard of care."

P1 data • Colorectal Cancer

A phase 1b/2 study of Nelmastobart with Capecitabine in Patients with Refractory mCRC (SITC 2025) - "Background Patients with metastatic colorectal cancer (mCRC) who are refractory to or intolerant of oxaliplatin and irinotecan have few effective treatment options.1 2 Nelmastobart, a humanized monoclonal antibody targeting Butyrophilin 1A1 (BTN1A1), has shown preclinical and clinical antitumor activity with immunomodulatory effects.3 This study evaluated the safety and efficacy of Nelmastobart combined with capecitabine in patients with refractory mCRC.Methods This multicenter, open-label, phase 1b/2 study included a dose-escalation safety lead-in followed by dose expansion. These findings support further evaluation in larger, randomized trials, with an emphasis on biomarker-driven patient selection strategies.Acknowledgements This study was supported by grants and research funds from STCube Pharmaceutical.Trial Registration NCT05990543Ethics Approval This study was approved by the IRB of Korea University Anam Hospital under the designation 2023AN0515.Consent Written..."

Clinical • Late-breaking abstract • P1/2 data • Colorectal Cancer • Oncology • BTN1A1

Nelmastobart Combination Shows Excellent Tolerability and Early Antitumor Activity in Refractory mCRC (SITC 2025) - P1, P1/2 | "This abstract reports Phase 1b safety run-in results focusing on safety, pharmacokinetics (PK), and preliminary efficacy.Methods This Phase 1b safety run-in of the open-label Phase 1b/2 trial evaluates Nelmastobart with trifluridine/tipiracil and bevacizumab in patients with metastatic or recurrent CRC refractory or intolerant to oxaliplatin- and irinotecan-based therapy. The study was conducted in accordance with the Declaration of Helsinki and with all applicable laws and regulations of the locale and country where the study was conducted, and in compliance with Good Clinical Practice Guidelines. The number of the IRB approval is 2025AN0204.Consent In this study, we don't contain sensitive and identifiable information about patients."

Late-breaking abstract • Colorectal Cancer • Oncology • BTN1A1

BTN1A1 Blockade Enhances Chemotherapy-Induced Anti-Tumor Immunity in Preclinical Lung Cancer Models (SITC 2025) - "The most significant anti-tumor effect was observed with the triple combination of PBMC + Docetaxel + hSTC810, which markedly outperformed combinations involving atezolizumab. In zebrafish xenografts, hSTC810 + Docetaxel produced the greatest tumor regression without inducing observable toxicity or developmental delay.Conclusions Across three physiologically relevant NSCLC models, hSTC810 synergized with Docetaxel to suppress tumor growth by enhancing immune-mediated cytotoxicity. These findings support BTN1A1 as a viable immunotherapeutic target and justify clinical development of hSTC810 in combination with chemotherapy, particularly for patients with PD-L1-refractory or immune-desert NSCLC."

IO biomarker • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BTN1A1

BTN1A1 H-score and multiplex biomarker profiling predict clinical benefit from nelmastobart plus capecitabine in advanced colorectal cancer: Phase Ib/II study (ESMO 2025) - P1/2 | "High BTN1A1 H-score and enrichment of YAP1 + , SLFN11 + , and Ki-67/PD-L1 + subsets correlated with improved PFS, supporting their use as predictive biomarkers. These findings support the ongoing randomized phase II trial and highlight BTN1A1 inhibition as a promising biomarker-driven strategy for immune modulation in CRC."

Biomarker • Clinical • IO biomarker • Metastases • P1/2 data • Colorectal Cancer • Oncology • Solid Tumor • BTN1A1 • PD-L1 • SLFN11 • YAP1

BTN1A1-targeted immunotherapy enhances standard treatment efficacy in NSCLC and colorectal cancer: Insights from patient-derived organoids and zebrafish models (ESMO 2025) - "Treatment regimens included hSTC810 and anti–PD-L1 antibodies, administered alone or with chemotherapy (docetaxel for NSCLC; FOLFOX/FOLFIRI for CRC)...Our data support BTN1A1 as a promising therapeutic target for PD-L1–negative or chemo-resistant tumors and highlight the utility of PDOs and zebrafish models for translational immunotherapy research. Legal entity responsible for the study STCube Pharmaceuticals."

Clinical • IO biomarker • Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BTN1A1

The published abstract included…preclinical results of BTN1A1-targeted treatment for colorectal cancer and non-small cell lung cancer. [Google translation] (BioTimes) - "'A specific phenomenon of increased BTN1A1 expression was observed in both non-small cell lung cancer and colon cancer after chemotherapy,' and 'When nelmastobart was used in combination with chemotherapy (Folfox/Folpiri for colon cancer, docetaxel for non-small cell lung cancer), a superior anti-tumor effect was observed compared to nelmastobart alone'."

Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer

STCube…announced on the 16th that it had received approval from the Ministry of Food and Drug Safety for a phase 2 clinical trial plan (IND) for nelmastobart for patients with advanced/metastatic non-small cell lung cancer. [Google translation] (BioTimes) - "With this IND approval, STCube is preparing to enroll patients, aiming to initiate the first dose within the year."

New P2 trial • Non Small Cell Lung Cancer

STCube demonstrates superiority over standard treatment in metastatic colorectal cancer. [Google translation] (BioTimes) - "A median PFS of 6.3 months was observed in patients with a BTN1A1 H-Score of 250 or higher (high-expression group, n=3), while mPFS was 4.2 months and 4.0 months in patients with a BTN1A1 H-Score of 150 to 249 (n=7) and less than 150 (n=15), respectively. No new safety issues were observed in these patients, and the combination therapy was generally well tolerated."

P1/2 data • Colorectal Cancer

...the company will present new preclinical and clinical findings at two upcoming international events -- the European Society for Medical Oncology (ESMO) Congress in October and the Society for Immunotherapy of Cancer (SITC) meeting in November (Korea Biomedical Review) - "The studies highlight BTN1A1 as a novel immune checkpoint target with therapeutic potential in colorectal cancer (CRC) and NSCLC....The first abstract...evaluates combination strategies using patient-derived organoids and zebrafish models to demonstrate how BTN1A1 blockade could improve standard treatments....The second abstract focuses on translational biomarker research from an investigator-initiated phase 1b/2 trial in metastatic colorectal cancer."

P1/2 data • Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer

BTN1A1 and Nuclear YAP1 Co-Expression as Predictive Biomarkers for Nelmastobart Efficacy in Lung Cancer: Findings From a Phase 1 Trial (IASLC-WCLC 2025) - "Conclusions : Preliminary results from the TMA analysis and Phase 1 trial suggest that targeting BTN1A1 with Nelmastobart is safe and shows early signs of clinical activity in lung cancer, particularly among patients with high nuclear YAP1 expression. These findings support further investigation in larger, biomarker-enriched clinical trials to validate BTN1A1 and YAP1 as predictive biomarkers and confirm the therapeutic efficacy of Nelmastobart in lung cancer."

Biomarker • Clinical • IO biomarker • P1 data • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor • BTN1A1 • CD8 • YAP1

hSTC810: Combination of Nelmastobart and Capecitabine Therapy in Metastatic Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=59 | Active, not recruiting | Sponsor: Korea University Anam Hospital | Not yet recruiting ➔ Active, not recruiting | Phase classification: P1b/2 ➔ P1/2 | Trial completion date: Mar 2026 ➔ Dec 2026

Enrollment closed • Phase classification • Trial completion date • Colorectal Cancer • Oncology • Solid Tumor

STCube to present BTN1A1-targeted lung cancer data at WCLC 2025 (Korea Biomedical Review) - "The second abstract...demonstrated that co-expression of BTN1A1 and nuclear YAP1 correlates with improved outcomes....In an analysis of tissue samples from four lung cancer patients enrolled in the phase 1 trial (three with small cell lung cancer and one with NSCLC), patients positive for BTN1A1 and with high nuclear YAP1 expression showed longer progression-free survival (PFS)."

Biomarker • P1 data • Non Small Cell Lung Cancer

A Study of hSTC810 in Combination With Paclitaxel in Relapsed or Refractory Extensive Stage Small Cell Lung Cancer (clinicaltrials.gov) - P1/2 | N=10 | Terminated | Sponsor: STCube, Inc. | N=130 ➔ 10 | Trial completion date: Oct 2027 ➔ Aug 2025 | Recruiting ➔ Terminated; Company strategy

Enrollment change • Trial completion date • Trial termination • Lung Cancer • Oncology • Small Cell Lung Cancer • Solid Tumor

STCube to present BTN1A1-targeted lung cancer data at WCLC 2025 (Korea Biomedical Review) - "The first abstract...reported that BTN1A1 expression increases following chemotherapy with docetaxel, thereby enhancing response to nelmastobart...Using patient-derived organoid models, STCube researchers found that BTN1A1 and PD-L1 are differentially expressed in NSCLC, and that docetaxel treatment specifically upregulated BTN1A1....This increase led to greater responsiveness to anti-BTN1A1 therapy compared with anti-PD-L1 therapy."

Preclinical • Non Small Cell Lung Cancer

STCube (052020) announced on the 12th that it has initiated phase 2 clinical trials after the combination therapy of nelmastobart, trifluridine-tipiracil (TAS-102), and bevacizumab passed all safety evaluations without dose-limiting toxicity (DLT) in phase 1b clinical trials targeting patients with refractory colorectal cancer. [Google translation] (BioTimes) - "Phase 2 patient dosing has begun at Korea University Anam Hospital, and patient enrollment is expected to expand to multiple institutions, including Seoul Asan Medical Center, Bundang Seoul National University Hospital, Seoul National University Hospital, and Severance Hospital in Sinchon, during the third quarter of this year."

Trial status • Colorectal Cancer

STCube submits phase 2 clinical trial application in Korea for anti-BTN1A1 immune checkpoint inhibitor Nelmastobart in NSCLC [Google translation] (BioNews) - "The NSCLC clinical trial will enroll patients exhibiting BTN1A1 expression (Tumor Proportion Score (TPS) ≥50%) who have previously undergone targeted chemotherapy, platinum-based chemotherapy, or immunotherapy as first-line treatment but now require second-line or subsequent therapeutic options. The study plans to recruit a total of 62 participants across seven medical institutions in Korea, including Samsung Medical Center....The primary efficacy endpoint of the trial is progression-free survival (PFS), with secondary endpoints encompassing overall survival (OS), objective response rate (ORR), disease control rate (DCR), and duration of response (DoR)."

New P2 trial • Non Small Cell Lung Cancer

...voluntary withdrawal of its previously approved Phase 1b/2 clinical trial targeting relapsed or refractory extensive-stage small cell lung cancer, which had received approval from the US Food and Drug Administration (FDA) and the MFDS. [Google translation] (BioNews) - "STCube stated that this strategic decision aims to strengthen the feasibility of biomarker-driven clinical designs while concentrating development efforts on NSCLC and colorectal cancer indications, areas considered pivotal for validating BTN1A1 as a novel immuno-oncology target."

IND • Small Cell Lung Cancer

Nelmastobart in Combination With Trifluridine/ Tipiracil and Bevacizumab in Metastatic/ Recurrent Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=52 | Recruiting | Sponsor: STCube, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Colorectal Cancer • Oncology • Solid Tumor

STCube begins patient dosing in combo trial for immunotherapy-resistant colorectal cancer (Korea Biomedical Review) - "STCube has kicked off patient dosing in a phase 1b/2 trial of its experimental immunotherapy nelmastobart, marking the first clinical use of BTN1A1 as a biomarker in microsatellite stable (MSS) colorectal cancer -- a notoriously immunotherapy-resistant subtype...The Korean biotech said Friday that two patients in the first cohort received nelmastobart at 800 mg in combination with trifluridine-tipiracil at 35 mg/m² and bevacizumab at 5 mg/kg....The trial enrolls patients who are refractory or intolerant to standard oxaliplatin- and irinotecan-based chemotherapies....A phase 2 expansion is planned for 52 patients with high BTN1A1 expression."

Trial status • Colorectal Cancer

Nelmastobart in Combination With Trifluridine/ Tipiracil and Bevacizumab in Metastatic/ Recurrent Colorectal Cancer (clinicaltrials.gov) - P1/2 | N=52 | Active, not recruiting | Sponsor: STCube, Inc. | Not yet recruiting ➔ Active, not recruiting

Enrollment closed • Colorectal Cancer • Oncology • Solid Tumor