An Exploratory Study of QL1706 in Combination With Chemotherapy for the Perioperative Treatment of Non-Small Cell Lung Cancer
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 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.