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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
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.
Peking Union Medical College Hospital, Chinese Academy of Medical Sciences
Beijing, Beijing Municipality, China
RECRUITINGPercentage of participants with major pathological response (MPR)
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.
Time frame: Perioperative/Periprocedural (Day of surgery)
Percentage of participants with pathological complete response (pCR)
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.
Time frame: Perioperative/Periprocedural (Day of surgery)
Safety and Tolerability
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.
Time frame: From first dose (Day 1) through 30 days after surgery
Percentage of participants with R0 resection
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.
Time frame: Perioperative/Periprocedural (Day of surgery)
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