NIPH Clinical Trials Search

A Phase II Investigator-Initiated Clinical Trial Evaluating the Efficacy and Safety of Combination Therapy with a PAI-1 Inhibitor (TM5614) and Immune Checkpoint Inhibitor Consolidation Therapy following Chemoradiotherapy for Locally Advanced Non-Small Cell Lung Cancer (TM-Alliance study)

Basic Information

Recruitment status	Recruiting
Health condition(s) or Problem(s) studied	non-small cell lung cancer
Date of first enrollment	06/04/2026
Target sample size	27
Countries of recruitment
Study type	Interventional
Intervention(s)	Continuous administration of TM5614 tablets (180 mg/day, given as three 60-mg tablets) will be maintained during the chemoradiotherapy phase (6 weeks) and the subsequent consolidation therapy phase (maximum of 1 year [52 weeks]).

Outcome(s)

Primary Outcome

1-year progression-free survival (PFS) rate

Secondary Outcome

Response Rate Disease Control Rate Progression Free Survival Overall Survival 1 year overall survival Progression free survival from the initiation of consolidation therapy. Overall survival from the initiation of consolidation therapy. 1 year progression free survival rate from the initiation of consolidation therapy. 1 year overall survival rate from the initiation of consolidation therapy. Incidence of new distant metastasis and local recurrence during the consolidation therapy phase Response rate to chemoradiotherapy Disease control rate of chemoradiotherapy Transition rate to consolidation therapy 1 year progression free survival rate assessed by independent central review Incidence of adverse events Incidence of Grade 2 or higher pneumonitis Evaluation of pulmonary function prior to the start of treatment, at the time of tumor assessment, every 3 cycles from the start of consolidation therapy, and 28 days after the last dose of study drug

Key inclusion & exclusion criteria

Age minimum	>= 18age old
Age maximum	<= 80age old
Gender	Both
Include criteria	1.Age 18 to 80 years at registration. 2.Written informed consent obtained from the patient to participate in this trial. 3.Patients with histologically (resection specimen, biopsy) or cytologically confirmed non-small cell lung cancer. 4.Patients diagnosed with unresectable clinical stage III disease (UICC-TNM classification, 9th edition) meeting at least one of the following criteria 1)-4), after undergoing all of the following imaging tests: contrast-enhanced chest CT, contrast-enhanced upper abdominal CT, FDG-PET (or PET/CT), bone scintigraphy, and contrast-enhanced brain CT (or contrast-enhanced brain MRI). Postoperative recurrence is excluded from this trial. 1)Tumor directly invading the parietal pleura, chest wall, pericardium, phrenic nerve, azygos vein, thoracic nerve roots, or stellate ganglion, combined with N1. 2)Invasion of the mediastinum, thymus, trachea, carina, recurrent laryngeal nerve, vagus nerve, esophagus, diaphragm; invasion of the heart, great vessels (aorta, superior and inferior vena cava, intrapericardial pulmonary artery and vein), brachiocephalic artery, common carotid artery, subclavian artery, brachiocephalic vein, subclavian vein; invasion of the vertebral body, vertebral lamina, spinal canal, cervical nerve roots, brachial plexus; or separate tumor nodule(s) in a different ipsilateral lobe (part of T4), and N0-1. 3)Any T, N2-3. 4)Determined to be unresectable in consultation with a physician and a surgeon. 5.Patients with non-squamous cell carcinoma who are negative for activating EGFR mutations and ALK rearrangements. 6.Patients who are negative or unknown for ROS1 rearrangements, BRAF V600E mutations, MET exon 14 skipping mutations, HER2 mutations, RET rearrangements, and NTRK rearrangements (unknown includes untested, inadequate specimen, or test results not available at the time of registration). 7.Patients who are judged by a radiation oncologist to be eligible for radiotherapy using IMRT or 3D CRT according to the study treatment. 8.Absence of prior chemotherapy and radiotherapy for the lung cancer to be treated in this clinical trial. 9.If patients have a prior history of radiotherapy (including for other types of cancer), they must meet both criteria 1)and 2). 1)The hilum and mediastinum are not included in the radiation field. 2)Absence of prior radiation pneumonitis of Grade >= 2. 10.Patients with at least one measurable lesion as defined by RECIST version 1.1 on imaging performed within 28 days prior to the initiation of study treatment. 11.Patients with an Eastern Cooperative Oncology Group performance status of 0 or 1. 12.Patients with a life expectancy of at least 90 days at the time of obtaining informed consent. 13.Patients whose the latest laboratory test results, obtained within 7 days before enrollment (the same day of the week is acceptable), meet the following criteria. These laboratory values must be obtained without the administration of granulocyte colony-stimulating factor preparations or blood transfusion within 14 days (the same day of the week is allowed) prior to the test. 14. Female patients of childbearing potential (including those who are amenorrheic for medical reasons e.g., chemical menopause) who have a negative pregnancy test within 14 days before registration and agree to use double contraception and avoid breastfeeding from the time of informed consent for at least 5 months after the last dose. Male patients who agree to use contraception from the start of study treatment for at least 7 months after the last dose. 15. Patients who are willing and able to comply with the study procedures.
Exclude criteria	1. Patients with concurrent or a history of severe hypersensitivity reactions to other antibody therapies. 2. Patients with primary immunodeficiency, active autoimmune disease, or a history of chronic or recurrent autoimmune disease. However, patients with hypothyroidism controlled with hormone replacement therapy, or skin conditions not requiring systemic therapy are eligible for enrollment. 3. Patients with prior exposure to anti PD1 or anti PD L1 antibodies. 4. Patients receiving continuous systemic administration of corticosteroids at a dose of more than 10 mg/day prednisone equivalent. 5. Patients with another primary malignancy. 6. Patients with concurrent or a history of interstitial lung disease or pulmonary fibrosis diagnosed by imaging. 7. Patients with concurrent unilateral whole lung atelectasis. 8. Patients with active inflammatory bowel disease, diverticulitis, or symptomatic gastrointestinal ulcer disease. 9.Patients who have uncontrollable pericardial effusion, pleural effusion, or ascites requiring ongoing management. 10. Patients with uncontrolled tumor related pain 11. Patients with a history of transient ischemic attack or cerebrovascular accident within 180 days prior to registration. 12. Patients with a history of pulmonary embolism or deep vein thrombosis 13. Patients with any of the following cardiovascular diseases History of myocardial infarction within 6 months prior to registration Symptomatic arrhythmia requiring treatment 14. Patients with administration of radiopharmaceuticals within 56 days prior to registration (excluding administration for diagnostic purposes). 15. Patients testing positive for HIV antibody, HBsAg, or HCV antibody 16. Patients with a bleeding diathesis including those with uncontrolled bleeding or ongoing hemoptysis. 17. Patients who are pregnant, breastfeeding, or possibly pregnant. 18. Patients with an active infection requiring systemic therapy. 19. Patients with a fever of 38.0 degrees C or higher at registration. 20. Patients with uncontrolled diabetes mellitus. 21. Patients requiring or with a history of transplantation,excluding autologous transplantation. 22. Patients who have undergone major surgery within 4 weeks prior to registration, and for whom study treatment is accordingly deemed inappropriate. 23. Patients who have received a live vaccine within 30 days prior to registration. 24. Patients who are judged to lack the capacity to give informed consent due to conditions such as dementia.