A Prospective, Multicenter, Randomized Controlled Study on the Efficacy and Safety of Low-dose Carboplatin Combined With Nab-Paclitaxel and Delayed Administration of Serplulimab as First-line Treatment for Advanced Squamous Non-small Cell Lung Cancer

Inclusion criteria

• Sign a written informed consent before implementing any trial-related procedures;
• Age ≥18 years and ≤75 years;
• Histologically or cytologically confirmed locally advanced (IIIB-IIIC), metastatic, or recurrent (stage IV) squamous NSCLC (according to the 8th edition TNM lung cancer staging by the International Association for the Study of Lung Cancer and the American Joint Committee on Cancer), not suitable for surgery and radical concurrent chemoradiotherapy, and subjects who have not previously received systemic treatment;
• Unknown gene status, or known histological specimen gene status confirming no EGFR gene-sensitive mutations or ALK gene fusion variations;
• According to the Response Evaluation Criteria in Solid Tumors (RECIST 1.1), at least one measurable lesion on imaging. Lesions in previously irradiated fields can be considered measurable if confirmed to have progressed;
• No prior systemic anti-tumor treatment for advanced/metastatic disease. Subjects who previously received platinum-containing adjuvant/neoadjuvant chemotherapy, or radical chemoradiotherapy for progressed disease, may be included if disease progression or recurrence occurs at least 6 months after the last chemotherapy drug treatment;
• Subjects with asymptomatic or symptomatically stable brain metastases after local therapy are allowed to enroll if they meet the following conditions: measurable lesions outside the central nervous system; no central nervous system symptoms or no worsening symptoms within at least 2 weeks; no need for corticosteroid therapy, or corticosteroids discontinued within 7 days prior to first dose, or corticosteroid dose stable and reduced to ≤10 mg/day prednisone (or equivalent) within 7 days prior to first dose;
• Patients may receive palliative radiotherapy, but completion must be at least 7 days before the first dose of the study drug, and radiotherapy-related toxicities must recover to ≤ grade 1 (CTCAE 5.0);
• ECOG performance status 0-1;
• Expected survival >3 months;
• Sufficient organ function: subjects must meet the following laboratory criteria: Absolute neutrophil count (ANC) ≥1.5 x 10⁹/L without using granulocyte colony-stimulating factor in the past 14 days; platelet count ≥100 × 10⁹/L without transfusion in the past 14 days; hemoglobin >9 g/dL without transfusion or erythropoietin use in the past 14 days; total bilirubin ≤1.5 times the upper limit of normal (ULN); aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5 × ULN (for subjects with liver metastases, ALT or AST ≤5 × ULN is allowed); serum creatinine ≤1.5 × ULN and creatinine clearance (calculated using the Cockcroft-Gault formula) ≥60 ml/min; good coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤1.5 × ULN; normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. If baseline TSH is outside the normal range, subjects can still be included if total T3 (or FT3) and FT4 are within the normal range; myocardial enzyme spectrum within the normal range (subjects with isolated laboratory abnormalities deemed clinically insignificant by the investigator are also allowed to enroll).
• For female subjects of childbearing potential, a urine or serum pregnancy test must be conducted within 3 days before the first study drug administration (Cycle 1, Day 1) and the result must be negative. If the urine pregnancy test result cannot be confirmed as negative, a blood pregnancy test is required. Non-childbearing female subjects are defined as postmenopausal for at least 1 year, or having undergone surgical sterilization or hysterectomy.
• If there is a risk of pregnancy, all subjects (male or female) must use contraception methods with an annual failure rate of less than 1% throughout the entire treatment period until 120 days (or 180 days) after the last study drug administration.

Exclusion criteria

• Pathology is adenocarcinoma or small cell lung cancer (SCLC), including lung cancer mixed with SCLC and NSCLC;
• Received radiotherapy before the first study drug administration, meeting one of the following conditions: ≥30% of bone marrow received radiotherapy within 14 days before treatment; lung lesion radiotherapy with a dose >30Gy within 6 weeks before treatment (subjects must have recovered to grade 1 or below from previous radiotherapy toxicity, without the need for corticosteroid treatment, and no history of radiation pneumonitis); palliative radiotherapy completed within 7 days before the first study drug administration;
• Diagnosed with other malignancies other than NSCLC within 5 years before the first administration (excluding completely treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or completely resected carcinoma in situ);
• Currently participating in an interventional clinical study treatment or received other study drugs or investigational devices within 4 weeks before the first administration;
• Previously received the following therapies: anti-PD-1, anti-PD-L1, or anti-PD-L2 drugs, or drugs targeting another stimulatory or co-inhibitory T cell receptor (e.g., CTLA-4, OX-40, CD137);
• Received Chinese patent medicines or immunomodulatory drugs with anti-NSCLC indications (including thymosin, interferon, interleukin, excluding local use for pleural effusion control) for systemic treatment within 2 weeks before the first administration;
• Experienced active autoimmune disease requiring systemic treatment (e.g., disease-relieving drugs, corticosteroids, or immunosuppressive agents) within 2 years before the first administration. Alternative therapies (e.g., thyroid hormones, insulin, or physiologic corticosteroids for adrenal or pituitary insufficiency) are not considered systemic treatment;
• Receiving systemic corticosteroid treatment (excluding nasal, inhaled, or other local corticosteroids) or any other form of immunosuppressive therapy within 7 days before the first study drug administration; Note: The use of physiological doses of corticosteroids (≤10 mg/day of prednisone or equivalent) is allowed.
• Presence of clinically uncontrollable pleural effusion/ascites (subjects who do not require drainage or whose effusion does not significantly increase after stopping drainage for 3 days may be enrolled);
• Known history of allogeneic organ transplantation (excluding corneal transplantation) or allogeneic hematopoietic stem cell transplantation;
• Known allergy to the study drugs Serplulimab, Nab-Paclitaxel, carboplatin, or any of their excipients;
• Has not fully recovered from any toxicities and/or complications caused by prior interventions before starting treatment (i.e., ≤ Grade 1 or returned to baseline, excluding fatigue or alopecia);
• Known history of human immunodeficiency virus (HIV) infection (i.e., HIV 1/2 antibody positive);
• Untreated active hepatitis B (defined as HBsAg positive and HBV-DNA copy number above the detection limit); Note: Subjects with hepatitis B who meet the following criteria may also be enrolled: HBV viral load <1000 copies/ml (200 IU/ml) before first dosing; subjects should receive anti-HBV treatment throughout the study chemotherapy to prevent viral reactivation; for subjects who are anti-HBc (), HBsAg (-), anti-HBs (-), and HBV viral load (-), prophylactic anti-HBV therapy is not required, but close monitoring for viral reactivation is needed.
• Subjects with active HCV infection (HCV antibody positive and HCV-RNA levels above the detection limit);
• Received a live vaccine within 30 days before first dosing (Cycle 1, Day 1); Note: Receiving injectable inactivated vaccines for seasonal influenza within 30 days prior to first dosing is allowed; however, intranasal live attenuated influenza vaccines are not permitted.
• Pregnant or breastfeeding women;
• Presence of any serious or uncontrollable systemic disease, such as: significant and severe uncontrollable abnormalities in resting electrocardiogram in rhythm, conduction, or morphology, such as complete left bundle branch block, second degree or higher atrioventricular block, ventricular arrhythmia, or atrial fibrillation; unstable angina, congestive heart failure, chronic heart failure with New York Heart Association (NYHA) class ≥ 2; myocardial infarction within 6 months before enrollment; poorly controlled blood pressure (systolic >140 mmHg, diastolic >90 mmHg); history of non-infectious pneumonia requiring glucocorticoid treatment within 1 year before first administration, or current clinically active interstitial lung disease; active pulmonary tuberculosis; presence of active or uncontrolled infection requiring systemic treatment; clinically active diverticulitis, intra-abdominal abscess, gastrointestinal obstruction; liver diseases such as cirrhosis, decompensated liver disease, acute or chronic active hepatitis; poorly controlled diabetes (fasting blood glucose (FBG) >10 mmol/L); urinalysis showing proteinuria ≥ , and confirmed 24-hour urine protein quantification >1.0 g; presence of mental disorders making it impossible to comply with treatment;
• History or evidence of disease, treatment or abnormal laboratory test values that may interfere with trial results or prevent the subject from participating in the study, or any other condition which the researcher considers unsuitable for enrollment, or other potential risks that the researcher believes make participation in this study inappropriate.