Non-small-cell lung cancer
Conditions
Interventions
Treatment group:SHR-2554, oral administration, 350 mg, twice daily, every 3 weeks + adebelizumab, 1200 mg, intravenous infusion, with each 3-week period constituting one treatment cycle
administered on Day 1 of each cycle
Sponsors
Cancer Hospital Chinese Academy of Medical Sciences
Eligibility
Sex/Gender
All
Age
18 Years to 75 Years
Inclusion criteria
Inclusion criteria: 1. Aged 18–75 years at the time of signing the informed consent form; both men and women are eligible; 2. Recurrent/metastatic NSCLC confirmed by histology or cytology; 3. EGFR/ALK-negative; 4. Previous treatment with an immune checkpoint inhibitor followed by disease progression at least 3 months later; 5. Mutations in SWI/SNF complex proteins or related genes (e.g., BRG1 [SMARCA4] deletion, BRM [SMARCA2] deletion, INI1 [SMARCB1] deletion, ARID1A deletion, etc.) 6. ECOG Performance Status (PS): 0–1; 7. Patients must have at least one measurable lesion according to RECIST 1.1 criteria; 8. Normal function of major organs, i.e., meeting the following criteria: a) Complete blood count (CBC) (without blood transfusion or use of hematopoietic growth factors within the past 14 days): Hemoglobin (Hb) >=90 g/L; absolute neutrophil count (ANC) >= 1.5 × 10^9/L; platelets (PLT) >= 100 × 10^9/L; White blood cell count (WBC) >=4.0 × 10^9/L and = 50 mL/min; c) Coagulation function: Activated partial thromboplastin time (APTT), International Normalized Ratio (INR), and prothrombin time (PT) = 1.5×ULN; d) Doppler ultrasound assessment: Left ventricular ejection fraction (LVEF) >= 50%; 9. Expected survival >= 3 months; 10. Women of childbearing potential must have a negative pregnancy test (serum or urine) within 14 days prior to enrollment and must agree to use appropriate contraception during the observation period and for 3 months following the last administration of the study drug; for men, they must be surgically sterilized or agree to use appropriate contraception during the observation period and for 3 months following the last administration of the study drug;
Exclusion criteria
Exclusion criteria: 1. Untreated brain metastases (patients who have previously received treatment for brain metastases [radiotherapy or surgery] may be enrolled if the investigator determines that the disease has been stable for at least 4 weeks, systemic hormonal therapy [dose > 10 mg/day of prednisone or other equivalent hormones] has been discontinued, and the patient is asymptomatic); 2. Accompanied by meningeal metastases, spinal cord compression, etc.; 3. Clinical symptoms associated with pleural effusion, pericardial effusion, or ascites requiring drainage, or those who have undergone therapeutic drainage of serous cavity effusions within 2 weeks prior to randomization; 4. Interstitial pneumonia, drug-induced pneumonia, radiation pneumonitis requiring steroid treatment, or active pneumonia with clinical symptoms or severe pulmonary dysfunction; 5. Active pulmonary tuberculosis or a history of active pulmonary tuberculosis infection within =48 weeks prior to screening, regardless of treatment status; 6. A tendency to bleed or coagulation disorders. Clinically significant bleeding events within 12 weeks prior to screening or a clear tendency to bleed, such as gastrointestinal bleeding, hemorrhagic gastric ulcer, or baseline fecal occult blood test result of ++ or higher; current or recent (within 10 days prior to receiving the first dose of study drug) treatment with full-dose oral or parenteral anticoagulants or thrombolytic agents; 7. Human immunodeficiency virus (HIV) infection or known acquired immunodeficiency syndrome (AIDS); untreated active hepatitis (hepatitis B, defined as a positive hepatitis B surface antigen [HBsAg] test result, HBV-DNA = 500 IU/ml, and abnormal liver function; hepatitis C, defined as positive hepatitis C antibodies [HCV-Ab], HCV-RNA above the lower limit of detection of the assay method, and abnormal liver function) or co-infection with hepatitis B and hepatitis C; 8. Patients with any active autoimmune disease or a history of autoimmune disease (including but not limited to: uveitis, enteritis, hepatitis, hypophysitis, vasculitis, myocarditis, nephritis, hyperthyroidism, hypothyroidism [eligible if on hormone replacement therapy]); Patients with childhood asthma that has completely resolved and requires no intervention in adulthood, or those with vitiligo, may be included; however, patients requiring medical intervention with bronchodilators are ineligible; 9. Severe infection within 2 weeks prior to the first dose (e.g., requiring intravenous antibiotics, antifungal, or antiviral medications), or unexplained fever >38.5°C occurring during screening or prior to the first dose; 10. Arterial or venous thromboembolic events occurring within 6 months prior to enrollment, such as cerebrovascular accidents (including transient ischemic attacks, cerebral hemorrhage, and cerebral infarction), deep vein thrombosis, and pulmonary embolism; 11. History of clinically significant cardiovascular disease, including but not limited to: (a) congestive heart failure (NYHA class > 2); (b) unstable angina; (c) myocardial infarction occurring within 3 months prior to signing the ICF; (d) any supraventricular or ventricular arrhythmia requiring treatment or intervention; 12. History of or concurrent malignant neoplasms in other systems within the past 5 years (excluding cured basal cell carcinoma of the skin, cervical carcinoma in situ, and ovarian cancer); 13. Receipt of a prophylactic or attenuated vaccine within 4 weeks prior to the
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Objective response rate, ORR; | — |
Secondary
| Measure | Time frame |
|---|---|
| Progression-Free Survival, PFS ;Overall Survival, OS;Duration of Response, DoR;Disease control rate, DCR;Safety; | — |
Countries
China
Contacts
Public ContactZhijie Wang
Cancer Hospital Chinese Academy of Medical Sciences
Outcome results
None listed