This study aims to evaluate the major pathologic response (MPR) rate of neoadjuvant therapy with sintilimab (PD-1 inhibitor) + IBI310 (anti-CTLA-4 antibody) + chemotherapy, and to assess the efficacy of this treatment strategy in patients with PD-L1-negative stage II - IIIB (excluding N3) NSCLC (according to AJCC 9th) scheduled for surgery.
The patient shall sign the informed consent.
Age ≥ 18 years.
Histologically or cytologically confirmed non-small-cell lung cancer (NSCLC).
No prior anticancer therapy, including (but not limited to) chemotherapy, immunotherapy or radiotherapy. Traditional Chinese medicine given for anticancer intent is permitted provided it was discontinued ≥ 2 weeks before first dose.
Major thoracic or abdominal surgery within 28 days before first dose or incomplete recovery from previous surgery.
Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids >10 mg/day) or other immunosuppressive agents for ≥ 7 consecutive days within 14 days before first dose. Except for inhaled or topical corticosteroids, or corticosteroid therapy at physiological replacement doses for adrenal insufficiency; short- courses (<7 days) corticosteroid use is permitted for the prevention or treatment of non-autoimmune conditions;
Participants who received live vaccines (including live attenuated vaccines) within 28 days before first dose.
Current or prior interstitial pneumonia or pulmonary diseases requiring systemic glucocorticoids.
Single group
sintilimab+IBI310+chemotherapy
Drug1. Neoadjuvant therapy phase: four planned doses of sintilimab 200 mg intravenous infusion at weeks -12, -9, -6, and -3 (Q3W); one planned dose of IBI310 1 mg/kg intravenous infusion at week -12; four planned doses of chemotherapy at weeks -12, -9, -6, and -3 (Q3W). Non-squamous NSCLC: pemetrexed 500 mg/m² IV over 30 min and carboplatin AUC 5 IV over 120 min or per institutional standard. Squamous NSCLC: nanoparticle albumin-bound paclitaxel 260 mg/m² IV over 30 min and carboplatin AUC 5 IV over 120 min or per institutional standard. 2. Surgery phase: At least 3 weeks after the last dose of the study drug , participants deemed operable by the investigator will undergo surgery.
MPR Rate
Defined as the proportion of patients who have achieved major pathologic response (with ≤10% viable tumor cells) in all patients after surgery.
Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)
Incidence and severity of adverse events (according to CTCAE v6.0 criteria), severity and its relationship to the experimental treatment; any abnormal laboratory test results, vital signs and physical examination results, etc.
pCR Rate
Defined as the proportion of all patients who completed treatment and had no invasive viable tumor in both the primary tumor and the sampled lymph nodes after surgery.
Overall Response Rate (ORR)
The proportion of patients who have had a complete response (CR) or partial response (PR) (according to RECIST1.1) after the neoadjuvant therapy.
Event Free Survival (EFS)
The time from enrollment to first occurrence of progression, disease recurrence (including local and distant recurrence), or death from any cause is assessed according to RECIST v1.1.
Tumor microenvironment and biomakers exploration
Surgical samples after neoadjuvant therapy and whole blood samples from patients prior to treatment, after two treatment cycles, and before surgery will be collected for single-cell RNA sequencing and proteomic analysis to analyze the tumor microenvironment and to explore the correlation between biomarkers and efficacy and safety.
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