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
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 54
- 试验地点
- 1
- 主要终点
- MPR Rate
研究概览
简要总结
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.
详细描述
Eligible patients were investigator - determined surgical candidates with resectable stage II-IIIB NSCLC, negative PD-L1 expression, no evidence of distant metastasis , and no evidence of unresectable localized tumor extension.
This study plans to enroll 54 patients.Patients are scheduled to receive one preoperative dose of sintilimab plus IBI310 combined with chemotherapy and three doses of sintilimab combined with chemotherapy as neoadjuvant therapy. Surgery will be performed on patients deemed operable by the investigator at least 3 weeks after the last dose of study drug. Following surgery, the investigator will assess the patient's response. Postoperatively, patients may continue receiving standard adjuvant therapy with PD-1 inhibitor for one year.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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.
- •Investigator-assessed resectable Stage II-IIIB (N3 excluded) NSCLC per AJCC 9th.
- •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.
- •PD-L1 expression negative (22C3 or E1L3N).
- •ECOG performance status 0 or
- •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.
- •Fertile female must have a negative serum pregnancy test within 7 days before first dose.
- •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.
排除标准
- •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.
- •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.
- •Other malignancy within 5 years before first dose, except for tumors assessed by the investigator as cured.
- •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
- •History of allogeneic haematopoietic stem-cell or solid-organ transplantation.
- •Hypersensitivity to antibody therapies (≥ grade 3 NCI-CTCAE v6.0), history of anaphylaxis, uncontrolled asthma, or significant drug allergies.
- •Pregnancy or lactation.
- •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.
研究组 & 干预措施
sintilimab+IBI310+chemotherapy
- 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 and carboplatin AUC 5 IV. Squamous NSCLC: nab paclitaxel 260 mg/m² IV and carboplatin AUC 5 IV. 2. Surgery phase: At least 3 weeks after the last dose of the study drug , participants deemed operable by the investigator will undergo surgery, and then can continue to receive standard adjuvant therapy for one year.
干预措施: sintilimab+IBI310+chemotherapy (Drug)
结局指标
主要结局
MPR Rate
时间窗: about 5 months after enrollment
Defined as the proportion of patients who have achieved major pathologic response (with ≤10% viable tumor cells) in all patients after surgery.
次要结局
- Incidence of Treatment-Emergent Adverse Events (Safety and Tolerability)(From the subject's written consent to participate in the study through 30 days after the final administration of the drug)
- pCR Rate(about 5 months after enrollment)
- Overall Response Rate (ORR)(12 weeks)
- Event Free Survival (EFS)(up to 5 years)
- Overall Survival (OS)(up to 5 years)
研究者
Chang Chen
MD, PhD
Shanghai Pulmonary Hospital, Shanghai, China