Non-Small Cell Lung Cancer
Conditions
Keywords
Neoadjuvant immunotherapy, QL1706, Immune checkpoint inhibitor, Non-Small Cell Lung Cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGQL1706 plus chemotherapy
QL1706, a bispecific anti-PD-1/CTLA-4 monoclonal antibody, is administered intravenously in combination with standard platinum-based chemotherapy as neoadjuvant treatment prior to surgery. Treatment is given for a planned number of cycles before surgical resection.
Sponsors
Peking Union Medical College Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with major pathological response (MPR) | Perioperative/Periprocedural (Day of surgery) | MPR is defined as ≤10% residual viable tumor cells in the resected primary tumor specimen (and resected lymph nodes if applicable) assessed by histopathologic review after neoadjuvant therapy. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of participants with pathological complete response (pCR) | Perioperative/Periprocedural (Day of surgery) | pCR is defined as 0% residual viable tumor cells in the resected primary tumor specimen (and resected lymph nodes if applicable) assessed by histopathologic review at definitive surgery. |
| Safety and Tolerability | From first dose (Day 1) through 30 days after surgery | Adverse events will be graded according to CTCAE v5.0 and summarized as the number and percentage of participants with any-grade TEAEs, grade ≥3 TEAEs, serious adverse events, and TEAEs leading to treatment discontinuation. |
| Percentage of participants with R0 resection | Perioperative/Periprocedural (Day of surgery) | R0 resection is defined as microscopically margin-negative resection (no tumor at the inked resection margin) on final surgical pathology after completion of neoadjuvant therapy. |
Countries
China
Contacts
CONTACTbinhe Tian
PRINCIPAL_INVESTIGATORHanping Wang, MD, PhD
Department of Pulmonary and Critical Care MedICIsne, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College
Outcome results
None listed