Lorlatinib-induced hypercholesterolemia
Conditions
Interventions
Test group:Recasimab
Sponsors
Hunan Cancer Hospital
Eligibility
Sex/Gender
All
Age
18 Years to 80 Years
Inclusion criteria
Inclusion criteria: 1. Age >= 18 years on the day of informed consent signature, with no restriction on gender; 2. Patients with unresectable stage IIIB/IIIC/IV NSCLC confirmed cytologically or histologically (staged per the 9th edition of the IASLC Staging Manual in Thoracic Oncology), who are not eligible for curative chemoradiotherapy; 3. ALK fusion positivity confirmed by genetic testing; 4. Grade 1–3 hypercholesterolemia adverse event (AE) occurring following lorlatinib treatment (per CTCAE Version 5.0); 5. Fasting triglyceride <= 5.6 mmol/L during the screening period; 6. Willing and able to comply with scheduled visits, treatment regimen, laboratory tests and other study procedures specified in the protocol.
Exclusion criteria
Exclusion criteria: 1. Subjects with known hypersensitivity to the investigational product, or those who have experienced severe hypersensitivity reactions to other antibody-based drugs; 2. Diagnosed with familial hypercholesterolemia according to the Simon Broome Criteria; 3. Received other PCSK9 inhibitors within 6 months prior to screening; 4. Uncontrolled hypercholesterolemia (total cholesterol above the upper limit of normal) existed prior to lorlatinib initiation; 5. Prior diagnosis of New York Heart Association (NYHA) class III–IV cardiac dysfunction; 6. 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 arterial disease, etc. 7. Prior diagnosis of severe arrhythmias, such as recurrent and symptomatic ventricular tachycardia, atrial fibrillation with rapid ventricular response; 8. Uncontrolled hypertension at screening or randomization (systolic blood pressure =160 mmHg and/or diastolic blood pressure =100 mmHg); 9. Prior diagnosis of diseases that substantially affect lipid profiles, including nephrotic syndrome, severe hepatic disease, Cushing’s syndrome, etc. 10. Prior diagnosis of type 1 diabetes mellitus, or uncontrolled type 2 diabetes mellitus at screening (HbA1c >8.5%); 11. Active infectious disease at screening, judged by the investigator to be ineligible for trial participation; 12. Participated in another interventional clinical trial within 1 month prior to screening (excluding screening failures), or still within 5 half-lives of the investigational drug at screening (whichever is longer); 13. History of drug addiction, substance abuse, or chronic alcohol abuse prior to screening; 14. Major surgery within 3 months prior to screening, or planned major surgery during the study period; 15. Long-term continuous or repeated systemic glucocorticoid use within 3 months prior to screening (excluding local administration: intra-articular, intranasal, inhaled, topical cutaneous use, etc. long-term continuous use defined as >=7 consecutive days; repeated use defined as cumulative use >=3 separate courses); 16. Received anti-obesity medications or underwent weight-altering surgery within 2 months prior to screening; 17. Any laboratory parameter meeting the following criteria at screening or randomization: a. Estimated glomerular filtration rate (eGFR) 3× upper limit of normal (ULN); for patients with liver metastases, ALT and AST 1.5× ULN; c. Creatine kinase (CK) >3× ULN; d. Thyroid-stimulating hormone (TSH) 1.5× ULN; e. Positive for human immunodeficiency virus antibody (HIV-Ab) or hepatitis C virus antibody (HCV-Ab); or 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 >= the assay lower limit); f. Positive pregnancy test; 18. Planned implantation of pacemaker, cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillator (ICD), or similar devices during the study period; 19. Positive HIV-Ab or HCV-Ab; or HBsAg-positive together with HBV-DNA =1000 copies/mL (or =200 IU/mL; if the assay lower limit exceeds 1000 copies/mL or 200
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The percentage change in LDL-C from baseline at Week 16 of treatment.; | — |
Secondary
| Measure | Time frame |
|---|---|
| Change from Baseline in LDL-C;LDL-C Target Attainment Rate;Safety Profile of Recaticimab; | — |
Countries
China
Contacts
Public ContactPu Xingxiang
Hunan Cancer Hospital
Outcome results
None listed