Non-small cell lung cancer
Conditions
Interventions
Safety run-in:Sacituzumab tirumotecan combined with definitive radiotherapy, followed by maintenance third-generation EGFR-TKI
Expansion cohort:Sacituzumab tirumotecan combined with definitive radiotherapy, followed by maintenance third-generation EGFR-TKI
Sponsors
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntarily sign a written informed consent form; 2. Male or female aged 18–75 at the time of signing the consent; 3. ECOG performance status score of 0 or 1; 4. Expected survival of at least 3 months; 5. Pathologically or cytologically confirmed locally advanced, unresectable stage III non-small cell lung cancer, as determined by the investigator; 6. Pathologically or cytologically confirmed EGFR-sensitive mutation positive (19del/L858R); 7. Subjects who have not received any form of prior systemic anti-tumor treatment; 8. At least one measurable lesion according to RECIST v1.1 (tumor lesion on CT scan >= 10 mm in longest diameter, lymph node lesion on CT scan >= 15 mm in short axis), suitable for repeated accurate measurement; 9. Major organ function sufficient to tolerate the treatment regimen; 10. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 3 days before the first dose (if the urine test is inconclusive, a serum test must be conducted, and the serum result prevails); 11. Female subjects of childbearing potential with male partners who are not sterilized must use highly effective contraception from the start of screening and agree to continue this for 120 days after the last study drug dose; periodic abstinence, safe period contraception, and withdrawal are not acceptable; 12. Male subjects who are not sterilized and have female partners of childbearing potential must use effective contraception from the start of screening until 120 days after the last dose; whether to stop contraception after this period should be discussed with the investigator.
Exclusion criteria
Exclusion criteria: Tumor-related features and treatment: 1. Patients with large cell carcinoma and mixed cell lung cancer, with small cell lung cancer components; 2. Have undergone any systemic or topical anti-tumor therapy for NSCLC, including cytotoxic drug therapy, immunotherapy, radiotherapy, investigational therapy, biologics, small molecule targeted therapy, etc.; 3. Simultaneous enrollment in another clinical study, unless it is a non-interventional clinical study or a follow-up period of an interventional study (defined as the first dose being at least 4 weeks after the last dose of the previous clinical study, or more than 5 half-lives of the study drug, whichever is shorter); 4. Palliative local treatment for non-targeted lesions within 2 weeks prior to the first dose; Non-specific immunomodulatory therapy (such as interleukin, interferon, thymosin, tumor necrosis factor, etc.) within 2 weeks prior to the first dose, excluding IL-11 used to treat thrombocytopenia; Received Chinese herbal medicine or proprietary Chinese medicines with antitumor indications within one week prior to the first dose; 5. History of alcohol allergy; 6. Those who have concerns about PET/CT scans; 7. Documented severe dry eye syndrome, severe meibomian gland disease, blepharitis, or a history of corneal diseases that hinder delayed corneal healing; 8. History of chest radiotherapy; 9. Individuals who have previously received chemotherapy or any EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment (including first-generation, second-generation, and third-generation EGFR-TKIs). Medical history and concomitants: 10. Malignant tumors other than NSCLC within the first 3 years prior to the first dose; Allow the inclusion of subjects with other malignancies who have been cured by local treatment, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, cervical or carcinoma in situ of the breast; 11. Having active autoimmune diseases requiring systemic treatment within 2 years prior to the first dose (such as symptom-improving drugs, corticosteroids, immunosuppressants) (excluding irAEs caused by PD-1/L1 inhibitors). Replacement therapies (such as thyroxine, insulin, or physiological corticosteroid replacement therapy for adrenal or pituitary insufficiency) are not considered systemic therapy; 12. Screening imaging indicates active pneumonia that is not controlled; 13. History of major illness within one year prior to first use, specifically: (1) Unstable angina, myocardial infarction, congestive heart failure (NYHA classification >=2) or vascular disease (such as aortic aneurysm at risk of rupture) or other cardiac damage that may affect the safety evaluation of the study drug within 12 months prior to the first dose (such as poorly controlled arrhythmias, myocardial ischemia, etc.); (2) History of esophageal and gastric varices, severe ulcers, unhealed wounds, abdominal fistula, intra-abdominal abscess, or acute gastrointestinal bleeding within 6 months prior to the first dose; (3) Any arterial thromboembolic event within 6 months prior to first administration, venous thromboembolic event of grade 3 or above as defined by NCI CTCAE 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy; (4) Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to the first dose; 14. History of gastrointestinal perforation and/or fistula, gastrointestinal obstruction (including incomplete i
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Dose-limiting toxicity (DLT) rate;Incidence of treatment-related grade ?= 3 adverse events;Objective response rate (ORR); | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall survival (OS);Time to first subsequent therapy (TFST);Progression-free survival (PFS);PET/CT quantitative parameters (SUVmax, TBR, ?SUVmax); | — |
Countries
China
Contacts
Public ContactTeng Feifei
Shandong First Medical University and Shandong Academy of Medical Sciences (Shandong Cancer Hospital &Institute)
Outcome results
None listed