Study on the Efficacy and Safety of JSKN016 as Neoadjuvant Therapy in Resectable Stage II-III Non-small Cell Lung Cancer Patients

Enrolled subjects were histologically confirmed resectable stage II, IIIA, and IIIB NSCLC (according to the 9th edition AJCC Lung Cancer TNM Staging System), with no evidence of distant metastasis and no evidence of unresectable local regional tumor extension.

Inclusion criteria

• The subject is able to understand the informed consent form, voluntarily participate in the study, and has signed the informed consent form.
• The subject is ≥18 years and ≤80 years of age on the day of signing the informed consent form; both males and females are eligible.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Histologically or cytologically confirmed resectable stage II, IIIA, or IIIB non-small cell lung cancer (NSCLC), according to the AJCC 9th edition TNM staging system for lung cancer.
• The subject has not previously received any anti-tumor therapy, including but not limited to systemic chemotherapy, immunotherapy, targeted therapy, or radiotherapy. Subjects who have received traditional Chinese medicine for anti-tumor indications are permitted to enroll provided a washout period of at least 2 weeks has elapsed.
• Tumor tissue genetic testing confirms NSCLC without EGFR sensitizing mutations (19del/L858R) and negative for ALK fusion genes.

Note: EGFR status may be determined using cytological or blood-based testing results. For subjects with squamous NSCLC, if EGFR and ALK status are previously unknown, testing is not required prior to enrollment in this study and will be considered negative.

• At least one measurable lesion at baseline according to RECIST version 1.1.
• Adequate organ function. The following laboratory test results must be obtained within 7 days prior to the first dose (echocardiography is permitted within 28 days prior to the first dose):

• Bone marrow function (no transfusion of whole blood or blood components within 14 days before the first dose; no hematopoietic growth factors within 7 days before the first dose):

Absolute neutrophil count ≥ 1.5 × 10⁹/L Hemoglobin ≥ 90 g/L Platelet count ≥ 100 × 10⁹/L

• Liver function:

Total bilirubin ≤ 1.5 × upper limit of normal (ULN) ALT and AST ≤ 3 × ULN

• Renal function:

Serum creatinine ≤ 1.5 × ULN, or creatinine clearance (Ccr) ≥ 50 mL/min calculated using the Cockcroft-Gault formula (see Appendix 4)

• Coagulation function:

International normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN Activated partial thromboplastin time (APTT) ≤ 1.5 × ULN

• Cardiac function:

Left ventricular ejection fraction (LVEF) ≥ 50% measured by echocardiography

• Pulmonary function:

Pulmonary function considered adequate for surgery as determined by the investigator.

• Female subjects of childbearing potential or male subjects whose partners are of childbearing potential must agree to use highly effective contraception from the time of signing the informed consent form until 24 weeks after the last dose. Female subjects of childbearing potential must have a negative serum or urine pregnancy test within 7 days prior to the first dose.
• The subject is able and willing to comply with study protocol requirements, including study visits, treatment plans, laboratory tests, and other study-related procedures.

Exclusion criteria

• Histopathological evidence of any small cell carcinoma component, or diagnosis of large cell neuroendocrine carcinoma or sarcomatoid carcinoma.
• Presence of another malignancy within 3 years prior to the first dose, except for tumors that have been clinically cured by local treatment and have an extremely low risk of recurrence (e.g., cutaneous squamous cell carcinoma, basal cell carcinoma of the skin, non-muscle-invasive bladder cancer, carcinoma in situ of the cervix, localized prostate cancer, etc.), or tumors with disease-free survival ≥ 3 years after curative treatment and an extremely low risk of recurrence or metastasis (e.g., ductal carcinoma in situ after radical surgery, papillary thyroid carcinoma after radical surgery, etc.).
• Insufficient washout from prior treatments before the first dose, including:

• Use of any investigational drug within 28 days prior to the first dose;
• Use of traditional Chinese herbal medicine or proprietary Chinese medicine with clear anti-tumor indications within 14 days prior to the first dose;
• Receipt of non-specific immunomodulatory therapy (e.g., interleukin, interferon, thymosin, tumor necrosis factor, etc.) within 14 days prior to the first dose;
• Requirement for systemic glucocorticoids (>10 mg/day prednisone or equivalent doses of other glucocorticoids) for more than 7 consecutive days, or immunosuppressive therapy, within 14 days prior to the first dose.

Exceptions include inhaled or topical corticosteroids, or physiologic replacement doses for adrenal insufficiency. Short-term (≤7 days) corticosteroid use is permitted for prophylaxis (e.g., prevention of contrast-agent allergy) or treatment of non-autoimmune conditions (e.g., delayed hypersensitivity due to allergen exposure);

• Major surgery (e.g., abdominal or thoracic surgery) within 28 days prior to the first dose, excluding minor procedures such as diagnostic puncture, implantation of infusion devices, or biliary stent placement, or anticipated need for major surgery during the study period;
• Receipt of live vaccines within 28 days prior to the first dose, or planned administration of live vaccines during the study period.
• Presence of interstitial lung disease (ILD) or risk factors related to non-infectious pneumonitis, including:

• History or current presence of ILD or non-infectious pneumonitis requiring systemic glucocorticoids or other immunosuppressive therapy;
• Suspected ILD or non-infectious pneumonitis that cannot be excluded by imaging during the screening period.
• Presence of active autoimmune disease requiring systemic treatment within the past 2 years (e.g., treatment with disease-modifying agents, corticosteroids, or immunosuppressive drugs).

Note: Replacement therapy (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered systemic treatment.

• Uncontrolled infections, including but not limited to:

• Active HBV or HCV infection. Patients positive for HBsAg must undergo HBV-DNA testing; if HBV-DNA exceeds the lower limit of detection of the local laboratory, enrollment is permitted provided antiviral therapy is administered.

Patients positive for HCV-Ab may be enrolled if HCV-RNA is negative;

• Severe infection within 4 weeks prior to the first dose, including but not limited to infections with complications requiring hospitalization, sepsis, or severe pneumonia; or active infection requiring systemic anti-infective therapy within 2 weeks prior to the first dose;
• History of immunodeficiency, positive HIV test, or history of acquired immunodeficiency syndrome (AIDS);
• Known active tuberculosis;
• Active syphilis.
• History of allogeneic bone marrow transplantation or organ transplantation.
• Known hypersensitivity to any component of the investigational drug, or a history of severe allergic reactions to other antibody-based therapies.
• Pregnant or breastfeeding women, or women planning to become pregnant during the study period.
• Known psychiatric disorders, substance abuse, alcohol abuse, or any other condition that, in the investigator's judgment, may affect the safety of study treatment or subject compliance.
• Any other disease, treatment, or laboratory abnormality, either past or present, that in the investigator's judgment may interfere with the evaluation of safety or efficacy, prevent full participation in the study, or make participation not in the subject's best interest.