NCT07472478尚未招募2 期
An Exploratory Phase II Clinical Study Protocol of Perioperative Treatment With Glesorasib Sequentially Combined With Ivonescimab and Chemotherapy for Resectable, Stage IB-IIIB, KRAS G12C-Mutant NSCLC
干预措施
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 入组人数
- 32
- 主要终点
- Pathologic complete response (pCR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy
研究概览
简要总结
This study is a multicenter, prospective, open-label clinical trial. It enrolls previously untreated patients with resectable stage IB-IIIB KRAS G12C mutation-positive NSCLC to evaluate the efficacy and safety of glesorasib sequentially combined with ivonescimab and chemotherapy as perioperative treatment for this patient population.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Sequential
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age Range: Males or females aged 18 years or older.
- •Diagnosis and Stage: Patients with histologically or cytologically confirmed resectable IB-IIIB NSCLC, staged according to the International Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology, 9th Edition.
- •Informed Consent: Patients must voluntarily participate in the study, provide written informed consent, and be willing to comply with follow-up procedures.
- •Prior Therapy: No prior systemic therapy for locally advanced or metastatic NSCLC (including adjuvant chemo/radiotherapy, neoadjuvant chemo/radiotherapy, definitive chemoradiotherapy, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, or anti-angiogenic therapy for locally advanced disease).
- •Mutation Status: KRAS G12C mutation positivity must be confirmed by next-generation sequencing (NGS) or polymerase chain reaction (PCR) testing.
- •Measurable Disease: At least one measurable target lesion as per RECIST v1.
- •Lesions previously treated with radiotherapy or other local-regional therapies cannot be considered target lesions unless clear progression has been documented post-radiotherapy. At baseline, the lesion must be ≥10mm in the longest diameter (≥15mm in short axis for lymph nodes) on CT or MRI and be suitable for accurate repeated measurement per RECIST v1.
- •Performance Status: Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or
- •Adequate Organ Function: Must meet the following criteria within 14 days prior to relevant tests, without transfusion or use of hematopoietic growth factors:
- •Platelets (PLT) ≥90 × 10^9/L
- •Hemoglobin (HGB) ≥90 g/L
- •Absolute Neutrophil Count (ANC) ≥1.5 × 10^9/L
- •Serum creatinine ≤1.5 × ULN or Creatinine Clearance (CrCl) ≥50 mL/min (calculated using the Cockcroft-Gault formula)
- •Alanine Aminotransferase (ALT), Aspartate Aminotransferase (AST) ≤2.5 × ULN (≤5 × ULN if liver metastases are present)
- •Total Bilirubin (TBIL) ≤1.5 × ULN (≤3 × ULN for patients with Gilbert's syndrome)
- •International Normalized Ratio (INR) or Prothrombin Time (PT) ≤1.5 × ULN, and Activated Partial Thromboplastin Time (APTT) ≤1.5 × ULN, or patients assessed by the investigator as having controlled bleeding tendency.
- •Urinalysis showing urine protein <2+ or 24-hour urinary protein quantification <1g.
- •Life Expectancy: Expected survival time ≥3 months.
- •Contraception: Fertile female subjects must agree to use effective contraception (e.g., IUD, oral contraceptives, condoms) during the study and for 6 months after study completion; have a negative serum pregnancy test within 7 days before enrollment; and must not be breastfeeding. Male subjects must agree to use effective contraception during the study and for 6 months after study completion.
排除标准
- •Prior Anti-Tumor Therapy:
- •Previous receipt of any anti-tumor therapy for lung cancer (including adjuvant chemoradiotherapy, neoadjuvant chemoradiotherapy, chemotherapy, radiotherapy, immune checkpoint inhibitors, targeted therapy, anti-angiogenic therapy, etc.).
- •Treatment with any other investigational drug within 28 days prior to the first dose in this study.
- •Treatment within 2 weeks prior to the first dose with NMPA-approved Chinese patent medicines explicitly indicated for anti-tumor purposes in their drug 说明书 (e.g., Compound Banmao Capsules, Kang'ai Injection, Kanglaite Capsules/Injection, Aidi Injection, Yadanzi Oil Injection/Capsules, Xiaoaiping Tablets/Injection, Huachansu Capsules, etc.).
- •Recent Surgery: Any surgery within 4 weeks prior to screening examinations.
- •Concurrent Primary Malignancy: Patients with a concurrent primary malignancy (except for adequately treated basal cell carcinoma of the skin, carcinoma in situ of the cervix, etc.).
- •Abnormal Organ Function: Meeting any of the following at screening:
- •Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≥ 1.5 times the upper limit of normal (ULN).
- •Creatinine clearance rate (CrCl) > ULN.
- •Hematological Abnormalities: Total white blood cell (WBC) count > 10.0 × 10^9/L or < 1.0 × 10^9/L at screening.
- •Significant Comorbidities: History of immunodeficiency diseases (e.g., HIV), other active cancers or malignancy history, autoimmune diseases, severe cardiovascular or cerebrovascular diseases, or any other diseases that may significantly reduce life expectancy.
- •Conditions Affecting Compliance: Any history of conditions that may affect protocol compliance (e.g., severe psychiatric disorders, cognitive dysfunction, drug abuse or addiction).
- •Pregnancy, Lactation, and Contraception: Pregnant or lactating women, or subjects of childbearing potential unwilling or unable to use effective contraception.
- •Allergy: Known allergy to any component of the study drug(s).
- •Recent Trial Participation: Participation in any drug clinical trial within 6 months prior to screening.
- •Investigator's Discretion: Any condition considered by the investigator as unsuitable for study participation.
- •Other Driver Mutations: Non-small cell lung cancer with other standard-therapy-eligible driver gene mutations (e.g., EGFR, ALK, BRAF V600E, HER-2, MET Exon 14, ROS1, RET, or NTRK1/2/3).
- •Central Nervous System (CNS) Metastases:
- •Symptomatic or progressive CNS metastases or carcinomatous meningitis.
- •Subjects with a history of brain metastases may be considered if they are clinically stable: no neurological symptoms, no corticosteroid treatment required, no indication for radiotherapy, and the largest diameter of the largest metastatic lesion on recent imaging is ≤ 1.5 cm.
- •Asymptomatic CNS metastases newly discovered during screening are allowed.
- •Subjects with a history of asymptomatic CNS metastases require confirmation of no progression via imaging scans performed at least 2 weeks apart.
- •Subjects with symptomatic CNS metastases may be considered if clinically stable after radiotherapy and/or surgery.
- •Subjects who underwent surgery for CNS metastases must have an interval of at least 4 weeks before the first study dose.
- •Asymptomatic subjects after CNS radiotherapy must have discontinued corticosteroids for at least 2 weeks prior to the first dose.
- •Cardiovascular Disease: Any of the following:
- •Congestive heart failure of New York Heart Association Class II or above.
- •Severe arrhythmia requiring medication.
- •Acute myocardial infarction, severe or unstable angina, coronary or peripheral artery bypass graft within 6 months prior to enrollment.
- •Left ventricular ejection fraction (LVEF) < 50%.
- •Prolonged QTcF interval ( > 470 ms for females, > 450 ms for males) or risk factors for Torsades de Pointes.
- •Uncontrolled hypertension (systolic BP ≥ 150 mmHg and/or diastolic BP ≥ 100 mmHg after antihypertensive therapy).
- •Thromboembolic Events: Arterial/venous thrombotic events within 6 months, hypertensive crisis, or hypertensive encephalopathy.
- •History of Epilepsy: Previous history of epilepsy.
- •Superior Vena Cava Syndrome: Presence of superior vena cava syndrome.
- •Pulmonary Disease: Active non-infectious interstitial lung disease, radiation pneumonitis, etc., active tuberculosis, pneumoconiosis, ≥ Grade 2 other pneumonias, or severely impaired pulmonary function at screening.
- •Severe Bone Lesions: Existing or potential severe bone damage from metastases, or uncontrolled bone pain.
- •Active Infection: Active or uncontrolled severe infection, or unexplained fever > 38.5°C.
- •Third-Space Fluid: Poorly controlled or drainage-requiring pleural effusion, ascites, or pericardial effusion. Subjects stabilized after treatment may be enrolled.
- •Tumor Invading Major Vessels: Imaging shows tumor invading or with unclear boundaries to major blood vessels.
- •Bleeding Risk: Evidence or history of bleeding tendency within 2 months before the first dose; history of hemoptysis, or unhealed wounds/ulcers/fractures within 2 weeks before the first dose.
- •Gastrointestinal Diseases: Known GI impairment or diseases significantly affecting drug absorption/metabolism, or major GI surgery affecting absorption.
- •Recent Live Vaccination: Administration of a live attenuated vaccine within 4 weeks before the first dose.
- •Severe Hypersensitivity to mAbs: History of severe hypersensitivity reaction to other monoclonal antibodies.
- •Autoimmune Disease: Active autoimmune disease requiring systemic treatment within 2 years before the first dose.
- •Immunosuppressive Therapy: Receiving systemic corticosteroids or other immunosuppressive therapy.
- •Viral Infections: Positive HIV antibody, or active viral hepatitis.
- •Active Hepatitis B or active Hepatitis C.
- •Carriers require antiviral therapy and monitoring during the study.
- •Active Syphilis.
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研究组 & 干预措施
Neoadjuvant therapy phase
Experimental
sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.
干预措施: Garsorasib (Drug)
Neoadjuvant therapy phase
Experimental
sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.
干预措施: Ivonescimab Combined With Chemotherapy (Drug)
Neoadjuvant therapy phase
Experimental
sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.
干预措施: Surgery (Procedure)
Neoadjuvant therapy phase
Experimental
sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.
干预措施: Ivonescimab (Drug)
Neoadjuvant therapy phase
Experimental
sequential preoperative regimen beginning with a 4- to 6-week lead-in phase of targeted monotherapy using Garsorasib (600 mg twice daily), followed by three cycles of combination chemoimmunotherapy comprising Ivonescimab (20 mg/kg), pemetrexed, and carboplatin, ultimately culminating in definitive surgical resection.
干预措施: Observation (Behavioral)
结局指标
主要结局
Pathologic complete response (pCR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy
时间窗: 14-24 weeks
次要结局
- Major Pathological Response (MPR) rate assessed according to the IASLC recommendations for pathologic evaluation of lung cancer neoadjuvant therapy(14-24 weeks)
- R0 resection rate(24 months)
- One-year event-free survival rate (1-y EFS%)(12 months)
- Objective Response Rate (ORR)(From initiation of neoadjuvant therapy until the final preoperative imaging assessment, up to 24 weeks (each cycle is 3 weeks).)
- Event-Free Survival (EFS)(From the date of first dose until the end of event-free status (disease progression, recurrence, or death from any cause), assessed up to 60 months.)
- Overall Survival(60 months)
研究者
Wen-zhao ZHONG
Principal Investigator
Guangdong Provincial People's Hospital
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