Anti-CTLA-4 plus sintilimab and chemotherapy before surgery for resectable Stage II–III NSCLC

Efficacy of Anti-CTLA-4 Antibody Combined With Sintilimab and Chemotherapy as Neoadjuvant Therapy for Resectable Stage II-III Non-Small Cell Lung Cancer: A Phase II, Single-Arm Clinical Study

This trial will test whether adding an anti-CTLA-4 antibody (IBI310) to sintilimab plus chemotherapy before surgery helps people with PD-L1–negative, resectable Stage II–III non-small cell lung cancer.

Quick facts

• Phase: Phase 2
• Study type: Interventional
• Enrollment: 54 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Shanghai Pulmonary Hospital, Shanghai, China (Academic / other)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone, sintilimab
• Locations: 1 site (Shanghai, Shanghai Municipality)
• Trial ID: NCT07410975 on ClinicalTrials.gov

What this trial studies

This Phase 2, single-center trial in Shanghai plans to enroll 54 patients with PD-L1–negative, resectable Stage II–IIIB (excluding N3) NSCLC. Participants receive one preoperative dose of sintilimab plus IBI310 with chemotherapy, then three further doses of sintilimab plus chemotherapy as neoadjuvant therapy before surgery, which is scheduled at least three weeks after the last dose. The primary efficacy endpoint is major pathologic response (MPR) at surgery, and investigators will also record surgical outcomes and postoperative assessments. After surgery, patients may receive standard adjuvant PD-1 inhibitor therapy for up to one year per investigator decision.

Who should consider this trial

Good fit: Adults (≥18) with investigator-confirmed, resectable Stage II–IIIB (N3 excluded) NSCLC, PD-L1 negative, ECOG 0–1, no prior systemic anticancer therapy, and no actionable driver mutations are the intended participants.

Not a fit: Patients with metastatic or unresectable disease, prior chemotherapy/immunotherapy, known actionable driver mutations (EGFR/ALK), PD-L1 positive tumors, or poor performance status are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could increase preoperative tumor kill (higher MPR) and potentially improve surgical outcomes and long-term prognosis for PD-L1–negative resectable NSCLC patients.

How similar studies have performed: Neoadjuvant PD-1 plus chemotherapy regimens have shown improved pathologic responses in prior studies (for example nivolumab-based regimens), but adding an anti-CTLA-4 antibody in this neoadjuvant setting is less well studied and evidence remains limited.

Eligibility criteria

INCLUSION CRITERIA

1. The patient shall sign the informed consent.
2. Age ≥ 18 years.
3. Histologically or cytologically confirmed non-small-cell lung cancer (NSCLC).
4. 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.
5. Investigator-assessed resectable Stage II-IIIB (N3 excluded) NSCLC per AJCC 9th.
6. Non-squamous NSCLC: no EGFR mutation, ALK rearrangement or any other driver mutation with an approved targeted agent. Squamous NSCLC: no known EGFR mutation, ALK rearrangement or other actionable driver mutation.
7. PD-L1 expression negative (22C3 or E1L3N).
8. ECOG performance status 0 or 1.
9. Adequate organ function within 7 days before first dose:

   * Haemoglobin ≥ 90 g/L (no transfusion within 28 days)
   * Absolute neutrophil count ≥ 1.5 × 10⁹/L
   * Platelet count ≥ 100 × 10⁹/L (no platelet transfusion or IL-11 within 14 days)
   * Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault)
   * Total bilirubin ≤ 1.5 × ULN (≤ 2.5 × ULN in Gilbert's syndrome or hepatic metastases)
   * ALT and AST ≤ 3 × ULN
   * INR or aPTT ≤ 1.5 × ULN
   * FEV\> 2L, FEV1\> 1L, FEV1/FVC ≥ 70%, DLCO ≥ 70% predicted; or Investigator determination that pulmonary reserve is adequate for planned surgery.
10. Fertile female must have a negative serum pregnancy test within 7 days before first dose.
11. Fertile female and male patients with female partners of childbearing potential must use a highly effective contraceptive method (annual failure rate \< 1 %) from 7 days before first dose until 24 weeks after the last dose.

EXCLUSION CRITERIA

1. Major thoracic or abdominal surgery within 28 days before first dose or incomplete recovery from previous surgery.
2. 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;
3. Participants who received live vaccines (including live attenuated vaccines) within 28 days before first dose.
4. Current or prior interstitial pneumonia or pulmonary diseases requiring systemic glucocorticoids.
5. Presence of any active autoimmune disease or history of autoimmune disease. Except in the following cases: Type 1 diabetes, stable hypothyroidism under hormone replacement therapy, psoriasis or vitiligo not requiring systemic treatment.
6. Other malignancy within 5 years before first dose, except for tumors assessed by the investigator as cured.
7. Uncontrolled comorbidities, including:

   * Active hepatitis B (HBsAg positive and HBV DNA \> 500 IU/mL or \> 2000 copies/mL) or hepatitis C (HCV antibody and HCV RNA positive). Subjects with HBV DNA ≤ 500 IU/mL who agree to antiviral prophylaxis are eligible.
   * Known HIV infection or history of AIDS.
   * Active tuberculosis.
   * Active infection requiring systemic antibiotics for \> 7 days within 28 days before first dose.
   * Clinically significant cardiovascular disease: cerebrovascular accident within 6 months, symptomatic heart failure (NYHA class II-IV), unstable angina or myocardial infarction within 6 months, risk of QTc prolongation or arrhythmia.
   * Urine protein qualitative≥ 2+, and 24-hour urine protein test \> 1g
8. History of allogeneic haematopoietic stem-cell or solid-organ transplantation.
9. Hypersensitivity to antibody therapies (≥ grade 3 NCI-CTCAE v6.0), history of anaphylaxis, uncontrolled asthma, or significant drug allergies.
10. Pregnancy or lactation.
11. Other conditions that may affect the safety or compliance of drug therapy in this study include, but are not limited to, psychiatric disorders, uncontrolled large serosal cavity effusions, or moderate to large serosal cavity effusions requiring repeated drainage (recurring within 2 weeks after intervention), such as pleural effusion, pericardial effusion, or ascites cachexia.

Where this trial is running

Shanghai, Shanghai Municipality

• Shanghai Pulmonary Hospital — Shanghai, Shanghai Municipality, China (Recruiting)

Study contacts

• Study coordinator: Chang Chen, MD

Conditions NSCLC Stage II; NSCLC Stage III; CTLA-4; NSCLC; neoadjuvant