Stage II-IIIB (N2) non-small cell lung cancer (NSCLC) with the following mutations: EGFR exon 20 insertion mutation, ALK fusion, ROS1 fusion, RET fusion, MET exon 14 skipping mutation, and KRAS G12C mutation
Conditions
Interventions
MET exon 14 skipping mutation group:Vebreltinib combined with Sacituzumab Tirumotecan
EGFR exon 20 insertion mutation group:Sunvozertinib combined with Sacituzumab Tirumotecan
ROS1 fusion mutation group:Unecritinib combined with Sacituzumab Tirumotecan
ALK fusion mutation group:Irualk combined with Sacituzumab Tirumotecan
KRAS G12C mutation group:Garsorasib combined with Sacituzumab Tirumotecan
RET fusion mutation group:Pralsetinib combined with Sacituzumab Tirumotecan
Sponsors
Zhejiang Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years and = 12 weeks. 3. Histologically or cytologically confirmed stage II-IIIB (N2) non-squamous non-small cell lung cancer (NSCLC) (8th edition of IASLC staging), deemed completely resectable by MDT evaluation. 4. Confirmed uncommon mutations in tumor tissue or blood samples by a nationally accredited laboratory, including EGFR exon 20 insertion mutation, ALK fusion, ROS1 fusion, RET fusion, MET exon 14 skipping mutation, and KRAS G12C mutation. Patients with additional actionable genomic alterations other than the above mutations require review by the study expert group to determine eligibility. 5. At least one measurable lesion per RECIST 1.1. Baseline tumor imaging assessment must be performed within 28 days before the first dose. 6. Women of childbearing potential must use effective contraception from screening until 3 months after stopping study treatment and must not breastfeed. A negative pregnancy test is required before dosing, or the subject must meet one of the following criteria to be considered not of childbearing potential: (1) Postmenopausal: aged > 50 years with amenorrhea for at least 12 consecutive months after stopping all exogenous hormone replacement therapy; (2) Aged = 12 consecutive months after stopping all exogenous hormone therapy and with luteinizing hormone (LH) and follicle-stimulating hormone (FSH) levels within the laboratory's postmenopausal reference range; (3) Status of irreversible sterilization, including hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (excluding tubal ligation). 7. Male subjects must use barrier contraception (condoms) from screening until 3 months after stopping study treatment. 8. Subject is voluntarily willing to participate and has provided written informed consent.
Exclusion criteria
Exclusion criteria: 1. Subjects shall not be enrolled in this study if they meet any of the following criteria: (1) Received any of the following prior treatments: 1) Prior pulmonary surgery; 2) Prior use of any EGFR tyrosine kinase inhibitor; 3) Prior systemic chemotherapy or immunotherapy for lung cancer; 4) Prior radiotherapy for lung cancer. (2) Underwent open major surgery at any site other than the lung within 14 days before the first dose of study drug. (3) Diagnosed with another malignancy within the past 5 years other than NSCLC, except completely resected basal cell carcinoma, carcinoma in situ of the bladder, or carcinoma in situ of the cervix. (4) Prior use of anti-tumor Chinese patent medicine. Subjects who used such medicine for =2 weeks before study treatment may be eligible. (5) Presence of severe or uncontrolled systemic diseases, including severe psychiatric/neurological disorders, epilepsy, dementia; unstable or decompensated respiratory, cardiovascular, hepatic, or renal disease; left ventricular ejection fraction (LVEF) =3 despite medical treatment); swallowing dysfunction, active gastrointestinal disorders, or other conditions significantly affecting absorption, distribution, metabolism, or excretion of oral medications; history of subtotal gastrectomy. (6) Fever >=38.0°C or clinically significant active infection within 1 week; active pulmonary tuberculosis; active fungal, bacterial, and/or viral infection requiring systemic therapy. Active hepatitis B is defined as: HBsAg positive + HBV-DNA above upper limit of normal (ULN) with elevated ALT or requiring treatment per investigator judgment. (7) Active bleeding, newly diagnosed thrombotic disease, receiving therapeutic anticoagulation, or bleeding diathesis. (8) Clinically significant resting ECG abnormalities: complete left bundle branch block, second-degree or higher atrioventricular block, clinically significant ventricular arrhythmia or atrial fibrillation, unstable angina, congestive heart failure, NYHA class >=2. (9) Myocardial infarction, coronary/peripheral artery bypass grafting, or cerebrovascular accident within 3 months. (10) QTc interval on 12-lead ECG: >=450 ms (males), >=470 ms (females). (11) Risk factors for QTc prolongation or arrhythmia: heart failure, hypokalemia >= CTCAE (version 4.03) grade 2, congenital long QT syndrome, family history of long QT syndrome. (12) Use of any drugs known to prolong QTc interval within 2 weeks before first dose. (13) Inadequate bone marrow reserve or organ function (no corrective therapy within 1 week before testing): 1) Absolute neutrophil count 3×ULN; 5) AST >3×ULN; 6) Total bilirubin >1.5×ULN; 7) Creatinine >1.5×ULN or creatinine clearance <45 mL/min (Cockcroft-Gault formula); 8) Serum albumin <28 g/L. (14) Female subjects who are pregnant, breastfeeding, or planning pregnancy during the study. (15) History or current presence of clinically active interstitial lung disease; active pneumonia. (16) History of hypersensitivity to any active or inactive ingredient of afatinib, or to drugs with similar or same class as afatinib. (17) Severe or uncontrolled ocular disorders that may increase safety risk, or ocular abnormalities requiring surgery d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| MPR rate; | — |
Countries
China
Contacts
Public ContactJian Zeng
Zhejiang Cancer Hospital
Outcome results
None listed