This is a single-center, open-label, single-arm phase II exploratory study evaluating a perioperative regimen of iparomlimab and tuvonralimab (QL1706; a bispecific PD-1/CTLA-4 antibody) combined with platinum-based chemotherapy in patients with resectable or potentially resectable stage IIB-IIIB non-small cell lung cancer (NSCLC) without actionable driver alterations. Approximately 30 eligible participants will receive three 21-day cycles of neoadjuvant QL1706 plus chemotherapy, followed by surgical resection if feasible. After surgery, participants will be followed regularly to assess pathologic response, recurrence, survival outcomes, and safety, including immune-related adverse events. The primary efficacy endpoint is major pathologic response (MPR), defined as ≤10% residual viable tumor in the resected specimen. Secondary endpoints include event-free survival, overall survival, objective response rate, disease control rate, and R0 resection rate. Exploratory analyses will evaluate changes in the tumor immune microenvironment and peripheral immune profiles using tumor tissue and blood samples, including T-cell and B-cell receptor repertoire analyses and multi-omics profiling, with the goal of developing models to predict treatment benefit and immune-related toxicity risk.

Patients with stage IIB-IIIB NSCLC have a substantial risk of recurrence after surgery, and perioperative systemic therapy is used to improve long-term outcomes. Immune checkpoint blockade combined with chemotherapy has improved pathologic response rates in resectable NSCLC; however, a proportion of patients-especially those with low PD-L1 expression-may derive limited benefit from single-pathway blockade. QL1706 is a bispecific antibody targeting PD-1 and CTLA-4 intended to enhance antitumor immunity through dual checkpoint inhibition. This study explores the feasibility, pathologic response, and longer-term clinical outcomes of adding perioperative QL1706 to standard platinum-based chemotherapy in a resectable/potentially resectable population.

All participants will receive three cycles of neoadjuvant QL1706 plus chemotherapy every 21 days, followed by radiographic assessment and surgical evaluation. Safety will be monitored throughout treatment and for 28 days after the last dose, with special attention to immune-related adverse events. After surgery, participants will be followed for recurrence and survival. Tumor tissue and peripheral blood will be collected at protocol-defined timepoints for exploratory biomarker studies (e.g., PD-L1 and immune cell profiling, TCR/BCR repertoire sequencing, transcriptomic/proteomic analyses), aiming to characterize immune changes associated with response, resistance, and immune-related toxicities and to develop predictive models for benefit and risk.

Inclusion Criteria:

• Patients are eligible for enrollment in this study only if they meet all of the following inclusion criteria and none of the exclusion criteria:
• The subject voluntarily participates in the study, provides written informed consent, demonstrates good compliance, and is willing to cooperate with study procedures and follow-up.
• Age ≥18 years at the time of signing the informed consent form; sex not restricted.
• Histologically confirmed non-small cell lung cancer (NSCLC).
• At least one measurable lesion according to RECIST version 1.1 (measurable lesion defined as a longest diameter ≥10 mm on spiral CT scan, or lymph node with a short axis ≥15 mm).
• No prior systemic therapy or local treatment for NSCLC.
• TNM stage IIB to IIIB disease, assessed by surgeons as resectable or potentially resectable.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
• Pulmonary function within normal limits.
• Adequate hematologic and organ function, based on laboratory tests obtained within 14 days prior to initiation of study treatment (unless otherwise specified):
• Hematology (no blood transfusion, G-CSF, or corrective medications within 14 days prior to screening):

Hemoglobin ≥90 g/L

Absolute neutrophil count ≥1.5 × 10⁹/L

Platelet count ≥100 × 10⁹/L

Biochemistry (no albumin infusion within 14 days prior to screening):

ALT and AST ≤2.5 × upper limit of normal (ULN)

Total bilirubin ≤2.0 × ULN (this criterion does not apply to patients with confirmed Gilbert's syndrome)

- Renal function:

Serum creatinine ≤1.5 × ULN, or

Creatinine clearance (CrCl) >50 mL/min calculated using the Cockcroft-Gault formula:

Females: CrCl = ((140 - age) × weight (kg) × 0.85) / (72 × serum creatinine [mg/dL])

Males: CrCl = ((140 - age) × weight (kg) × 1.00) / (72 × serum creatinine [mg/dL])

• Women of childbearing potential must agree to remain abstinent (avoid heterosexual intercourse) or use highly effective contraception with a failure rate <1% per year during study treatment and for at least 6 months after the last dose.
• Women are considered of childbearing potential if they are menstruating, not postmenopausal (defined as ≥12 consecutive months of amenorrhea without other causes), and have not undergone sterilization (bilateral oophorectomy and/or hysterectomy).

Highly effective contraceptive methods include bilateral tubal ligation, male sterilization, ovulation-suppressing hormonal contraceptives, hormonal intrauterine devices (IUDs), and copper IUDs.

The reliability of sexual abstinence must be evaluated in relation to the duration of the clinical trial and the participant's lifestyle. Periodic abstinence (e.g., calendar method, ovulation method, basal body temperature method, post-ovulation method) and withdrawal are not acceptable methods of contraception.

- Male participants must agree to remain abstinent (avoid heterosexual intercourse) or use effective contraception and must agree not to donate sperm, as defined below:

If the female partner is of childbearing potential, male participants must remain abstinent or use condoms plus an additional contraceptive method with a failure rate <1% per year during treatment and for at least 6 months after the last dose, and must not donate sperm during this period.

If the female partner is pregnant, male participants must remain abstinent or use condoms during treatment and for at least 6 months after the last dose to avoid fetal exposure.

-The reliability of sexual abstinence must be evaluated relative to the study duration and participant's lifestyle. Periodic abstinence and withdrawal are not acceptable methods.

Exclusion Criteria:

Patients meeting any of the following criteria will be excluded from the study:

• Prior exposure to any immunotherapy.
• ECOG performance status >1.
• Evidence of distant metastasis or intrathoracic metastatic disease.
• Presence of actionable driver gene alterations with available targeted therapies, including but not limited to EGFR mutations, ALK fusions, ROS1 fusions, RET, NTRK, BRAF V600E mutations, or MET exon 14 skipping mutations.
• Pregnant women (positive pregnancy test prior to treatment) or breastfeeding women.
• Known hypersensitivity or intolerance to recombinant humanized PD-1 monoclonal antibodies or any of their components (or excipients).
• Major surgery (excluding biopsy) within 4 weeks prior to the first dose of study treatment, or incomplete wound healing from prior surgery.
• Clinically significant cardiovascular or cerebrovascular disease, including but not limited to:
• Acute myocardial infarction within 6 months prior to enrollment
• Severe or unstable angina
• Cerebrovascular accident or transient ischemic attack
• Congestive heart failure (New York Heart Association class ≥II)
• Arrhythmias requiring antiarrhythmic treatment (except beta-blockers or digoxin)
• QTc interval >480 ms on repeated ECG measurements
• Hepatic or renal insufficiency, including conditions such as jaundice, ascites, and/or:

Total bilirubin >3 × ULN

Urinary protein >3.5 g/24 hours or renal failure requiring hemodialysis or peritoneal dialysis

Urinalysis showing proteinuria ≥++ or confirmed 24-hour urinary protein >1.0 g

• Persistent active infection of grade >2 according to CTCAE version 5.0.
• Active autoimmune disease or history of autoimmune disease within the past 2 years, or known/suspected autoimmune disease that may affect vital organ function or require systemic immunosuppressive therapy, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis.
• Allowed conditions include type I diabetes mellitus, hypothyroidism requiring hormone replacement only, and skin diseases not requiring systemic treatment (e.g., vitiligo, psoriasis, alopecia), or conditions not expected to recur without external triggers.
• Replacement therapies (e.g., thyroxine, insulin, or physiological corticosteroid replacement for adrenal or pituitary insufficiency) are not considered systemic immunosuppressive treatment.
• Prior or planned solid organ transplantation or allogeneic bone marrow transplantation.
• Active tuberculosis (Mycobacterium tuberculosis) or other active infections.
• Known history of human immunodeficiency virus (HIV) infection.
• Severe non-healing wounds, ulcers, or fractures.
• History of substance abuse, or any medical, psychological, or social condition that may interfere with study participation, compromise compliance, or pose a safety risk.
• Unresolved toxicities > grade 1 from any prior therapy or procedure (CTCAE version 5.0), except for alopecia, anemia, or hypothyroidism.
• Objective evidence of severe pulmonary dysfunction, including history of severe pulmonary fibrosis, interstitial lung disease, pneumoconiosis, radiation pneumonitis, or drug-related pneumonitis.
• Concomitant malignancies or history of other malignancies within the past 5 years, except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, carcinoma in situ of the breast or cervix, treated superficial bladder cancer, or prostate adenocarcinoma treated surgically with prostate-specific antigen (PSA) within normal limits.
• Any condition that, in the investigator's judgment, makes the patient unsuitable for participation in this study.
• Concurrent participation in another clinical study.

At this time, plans for sharing individual participant data (IPD) have not been finalized.

Data sharing will be considered after study completion, data anonymization, and in accordance with institutional policies and ethical requirements. Requests for access may be reviewed by the study investigators on a case-by-case basis.