NSCLC
Conditions
Interventions
Test group:Neoadjuvant treatment with ivonescimab (AK112) + platinum-containing two-drug chemotherapy
Sponsors
Cancer Hospital Affiliated of Shandong First Medical University
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Voluntary signed written informed consent; Subjects must sign and date the IRB/IEC-approved informed consent form in accordance with the guidelines of the competent authority and the research organization. The informed consent must be signed prior to performing any protocol-related procedures that are not part of the subject's routine medical care. Subjects must be willing and able to comply with the visits, treatment regimens, laboratory tests, and comply with other requirements of the study as specified in the schedule. 2. age =18 years and =75 years at enrollment, both sexes; 3. Eastern Cooperative Oncology Group (ECOG) physical status score of 0 or 1; 4. expected survival = 3 months; 5. patients with non-small cell lung cancer diagnosed by histologic or cytologic pathology and resectable clinical stage II-IIIB (T3N2) (according to the 8th edition of TNM staging of lung cancer); 6. Clearly EGFR-sensitive mutation-positive (19del or L858R) by pathohistologic or cytologic testing; 7. No previous antitumor therapy of any kind. 8. have at least one measurable lesion according to RECIST v1.1, (=10mm long diameter on CT scan for tumor lesions and =15mm short diameter on CT scan for lymph node lesions according to RECIST 1.1 criteria) that is suitable for repeated accurate measurements; 9. subjects must have adequate cardiopulmonary function for the intended radical lung resection. 10. good organ function is determined by the following requirements: 1) Lung ventilation function test with FEV1 = 1.5L or expected FEV1 = 800ml after lobectomy/total lung resection; 2) Hematology (no supportive therapy with any blood component or cell growth factor within 7 days prior to initiation of study treatment): i. Absolute neutrophil ANC = 1.5 x 10^9/L; ii. platelet count = 100 x 10^9/L; iii. hemoglobin = 90 g/L 3) Renal: i. Serum creatinine (Cr) = 1.5 x upper limit of normal (ULN) or creatinine clearance* (CrCl) calculated value = 50 mL/min; *CrCl will be calculated using the Cockcroft-Gault formula; CrCl (mL/min) = {(140 - age) × body weight (kg) × F}/(SCr (mg/dL) × 72); where F = 1 for men and F = 0.85 for women; SCr = serum creatinine ii. urine protein <2+, or 24-hour (h) urine protein quantification <1.0 g 4) Liver: i. serum total bilirubin (TBIL) = 1.5 x ULN; TBIL = 3 x ULN for subjects with liver metastases or confirmed/suspected Gilbert's Syndrome; ii. AST and ALT = 2.5 x ULN; for subjects with liver metastases, AST and ALT = 5 x ULN; iii. serum albumin (ALB) = 28 g/L; 5) Coagulation: International Normalized Ratio (INR) with Partial Thromboplastin Time (PTT) or Activated Partial Thromboplastin Time (APTT) = 1.5 x ULN; 11. Patients who agree to undergo radical surgical treatment; 12. Patients with no contraindications to surgery as judged by a specialist physician 13. Female subjects of childbearing age with negative urine or serum pregnancy test results within 3 days prior to the first dose (if the urine pregnancy test results cannot be confirmed as negative, serum pregnancy test is required, and the serum pregnancy results shall prevail); 14.If a female subject of childbearing potential engages in sexual intercourse with a male partner who is not sterilized, that subject must be using a highly effective method of contraception from the start of screening and must agree to the continued use of these precautions up to 120 days after the last dose of study drug; cyclic abstinence, safe period contraception, and extracorporeal ejaculation a
Exclusion criteria
Exclusion criteria: Tumor-related features and treatment: 1. patients with large-cell and mixed-cell lung cancer, mixed with small-cell lung cancer components; 2. presence of locally advanced unresectable or metastatic disease; 3. all patients harboring other types of EGFR-sensitive mutations; 4. Any systemic or local antitumor therapy for NSCLC, including cytotoxic drug therapy, immunotherapy, radiotherapy, experimental therapy, biologics, and small molecule targeted therapy; 5. concurrent 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 time of the first dose being 4 weeks or more from the time of the last dose in the previous clinical study or 5 or more half-lives of the study drug, whichever is shorter); 6. Palliative local therapy for non-target lesions within 2 weeks prior to the first dose; non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymic peptide, tumor necrosis factor, etc., excluding IL-11 used to treat thrombocytopenia) within 2 weeks prior to the first dose; and herbal or proprietary Chinese medicine with an antitumor indication within 1 week prior to the first dose; Past medical history and co-morbidities: 7. malignancy other than NSCLC within 3 years prior to first dose; allows for the inclusion of subjects with other malignancies that have been cured by local therapy, such as basal or cutaneous squamous cell carcinoma, superficial bladder cancer, and carcinoma in situ of the cervix or breast; 8. active autoimmune disease (e.g., treatment with disease-modifying drugs, corticosteroids, immunosuppressants) requiring systemic therapy within 2 years prior to the first dose (excluding irAE resulting from the use of PD-1/L1 inhibitors). Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a systemic therapy; 9. history of major medical illness within 1 year prior to first dose, specifically: Unstable angina pectoris, myocardial infarction, congestive heart failure (New York Heart Association NYHA classification = grade 2) or vascular disease (e.g., aortic aneurysm with risk of rupture) requiring hospitalization, or other cardiac impairment (e.g., poorly controlled cardiac arrhythmia, myocardial ischemia, etc.) that may interfere with the evaluation of the safety of the investigational drug, within the 12 months prior to the first dose of study drug; History of esophagogastric fundal varices, severe ulcers, unhealed wounds, abdominal fistulas, intra-abdominal abscesses, or acute gastrointestinal bleeding within 6 months prior to first dose; Any arterial thromboembolic event, venous thromboembolic event of grade 3 or greater as defined by NCI CTCAE 5.0, transient ischemic attack, cerebrovascular accident, hypertensive crisis, or hypertensive encephalopathy within 6 months prior to first dose; ? Acute exacerbation of chronic obstructive pulmonary disease within 4 weeks prior to first dose; 10. history of gastrointestinal perforation and/or fistula within 6 months prior to the first dose, history of gastrointestinal obstruction (including incomplete intestinal obstruction requiring parenteral nutrition), extensive bowel resection (partial colectomy or extensive small bowel resection complicated by chronic diarrhea); 11. live or live attenuated vaccine administered within 4 weeks prior to the first dose or planned to be admi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Major Pathological response; | — |
Secondary
| Measure | Time frame |
|---|---|
| Pathological complete response;24m Event-free survival%;Event-free survival;Objective Response Rate;Surgery R0 Excision rate;Tumor downstaging rate;security; | — |
Countries
China
Contacts
Public ContactHaiyong Wang
Cancer Hospital Affiliated of Shandong First Medical University
Outcome results
None listed