Recaticimab for high cholesterol caused by lorlatinib in ALK-positive lung cancer

Who can take part

• Aged ≥ 18 years on the day of signing the informed consent form, with no gender restriction
• Patients with unresectable stage IIIB/IIIC/IV non-small cell lung cancer (NSCLC) confirmed by cytology or histology (staging defined per the 9th edition of the International Association for the Study of Lung Cancer (IASLC) Staging Manual in Thoracic Oncology)
• Positive ALK fusion confirmed by genetic testing
• Developed Grade 1-3 hypercholesterolemia adverse events after lorlatinib treatment (per CTCAE Version 5.0)
• Fasting triglyceride level ≤ 5.6 mmol/L at screening
• Willing and able to comply with scheduled study visits, treatment regimens, laboratory tests and all other study procedures

Who cannot take part

• Subjects with known hypersensitivity to the investigational product, or a history of severe hypersensitivity reactions to other antibody-based drugs
• Received other PCSK9 inhibitors within 6 months prior to screening
• Prior diagnosis of New York Heart Association (NYHA) Class III-IV cardiac dysfunction
• Prior diagnosis of atherosclerotic cardiovascular disease (ASCVD), including acute coronary syndrome, stable coronary artery disease, post-revascularization status, ischemic cardiomyopathy, ischemic stroke, transient ischemic attack, peripheral atherosclerotic artery disease, etc
• Prior diagnosis of severe arrhythmia, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response
• Prior diagnosis of diseases that significantly affect lipid levels, including nephrotic syndrome, severe liver disease, Cushing's syndrome, etc
• Participation in another interventional clinical trial within 1 month before screening (excluding screen failures), or within 5 half-lives of the investigational product at screening (whichever duration is longer)
• History of drug abuse, illicit substance use, or chronic alcohol abuse prior to screening
• Major surgery within 3 months before screening, or planned major surgery during the study period
• Chronic continuous or repeated systemic glucocorticoid use within 3 months prior to screening (topical administration excluded, e.g., intra-articular, intranasal, inhaled, cutaneous external use; chronic continuous use defined as ≥7 consecutive days; repeated use defined as cumulative administration ≥3 courses)
• Weight-loss medication use or weight-altering bariatric surgery within 2 months prior to screening
• Uncontrolled hypertension at screening or randomization (systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg)
• Active infectious disease at screening judged by the investigator to render the subject ineligible for trial participation
• Planned implantation of cardiac pacemaker, cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillator (ICD), or equivalent device during the study period
• Positive human immunodeficiency virus antibody (HIV-Ab) or hepatitis C virus antibody (HCV-Ab); positive hepatitis B surface antigen (HBsAg) with HBV-DNA ≥1000 copies/mL (or ≥200 IU/mL; if the assay lower limit exceeds 1000 copies/mL or 200 IU/mL, HBV-DNA ≥ assay lower limit)
• The investigator determines the subject has poor compliance or any other factor precluding trial participation, including but not limited to conditions placing the subject at unacceptable risk or likely confounding study results
• Prior diagnosis of Type 1 diabetes mellitus, or uncontrolled Type 2 diabetes mellitus at screening (HbA1c >8.5%)
• Any laboratory test value meeting the following criteria at screening or randomization:; Estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m² (calculated via the MDRD formula); Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 times the upper limit of normal (ULN); for patients with liver metastases, ALT/AST >5×ULN; or total bilirubin >1.5×ULN; Creatine kinase (CK) >3×ULN; Thyroid-stimulating hormone (TSH) below the lower limit of normal (LLN) or >1.5×ULN; Positive human immunodeficiency virus antibody (HIV-Ab) or hepatitis C virus antibody (HCV-Ab); positive hepatitis B surface antigen (HBsAg) with HBV-DNA ≥1000 copies/mL (or ≥200 IU/mL; if the assay lower limit exceeds 1000 copies/mL or 200 IU/mL, HBV-DNA ≥ assay lower limit); Positive pregnancy test
• Diagnosed with familial hypercholesterolemia per the Simon Broome Criteria
• Uncontrolled hypercholesterolemia (total cholesterol above the upper limit of normal) existed before lorlatinib initiation
• Judged by the investigator to be unsuitable for subcutaneous injection