Combined Statin and PD-1/PD-L1 Inhibitors in Treating Non-small Cell Lung Cancer

The Fourth Affiliated Hospital of Zhejiang University School of Medicine

Status

Active, not recruiting

Conditions

Lung Cancer

Treatments

Drug: immunotherapy

Study type

Observational

Funder types

Other

Identifiers

NCT05636592

K2022145

Details and patient eligibility

About

This prospective observational study was designed to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in combination with statins compared with treatment with PD-1/PD-L1 inhibitors alone in advanced NSCLC patients. Participants will receive either immunotherapy + statin or immunotherapy until progressive disease (PD) as assessed by the investigator using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1). Treatment can be continued until persistent radiographic PD or symptomatic deterioration.

Full description

Statin is an inhibitor of 3-hydroxy-3-methylglutaryl-coenzyme A (CoA) reductase (HMGCR), the rate-limiting enzyme of the mevalonate (MVA) pathway for the cholesterol biosynthesis. Statins reportedly target the immune microenvironment through cytokines or chemokines and immune checkpoints. In a B16 melanoma lung metastatic model, statin lowers PD-1 expression in CD8+ T cells and effectively restores antitumor activity. In colorectal cancers model, simvastatin acts as a potential therapeutic drug for immunotherapy, which suppresses lncRNA SNHG29-mediated YAP activation and promotes anti-tumor immunity by inhibiting PD-L1 expression. Some retrospective observational studies have reported that baseline statin use was associated with improved clinical activity of PD-1/PD-L1 inhibitors in non-small cell lung cancer (NSCLC) patients. These findings support the adjuvant role of statins combined with immunotherapy. Statin therapy may be a combination tool for cancer immunotherapy in patients with NSCLC. Data from already completed clinical trials are not always supportive. These findings should be validated in further prospective studies with larger sample sizes. More clinical trials are needed to explore the right drug type, dose, frequency, duration, and suitable participator. Thus, this prospective observational study was designed to evaluate the safety and efficacy of PD-1/PD-L1 inhibitors in combination with statins compared with treatment with PD-1/PD-L1 inhibitors alone in advanced NSCLC patients.

Enrollment

250 estimated patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Histopathology or hemology diagnostics of phase IIIB or IV (AJCC Version 8) NSCLC that cannot be surgicalor-able or radiotherapy
Not applicable to EGFR/ALK/ROS1 targeted therapy
Within 4 weeks prior to randomization, at least one measurable target lesions assessed by irRC in accordance with RECIST 1.1 requirements
Patients have never received PD-1/PD-L1/CTLA-4 inhibitors treatment throughout the body for phase IIIB or IV NSCLC
Patient have indications for statins
The ECOG PS score for 7 days prior to the first drug use of the study drug was 0 or 1
The expected lifetime is more than 12 weeks
The main organ function sits well, i.e. meets the following criteria (no blood transfusion, albumin, recombinant human platelet production or Colony-stimulating factor (CSF) treatment within 14 days prior to the first drug use in this study)

Exclusion criteria

Within 5 years or at the same time, there are other active malignancies. Cured limited tumors, such as skin base cell carcinoma, skin squamous carcinoma, superficial bladder cancer, prostate in situ cancer, cervical in situ cancer, etc. can be included in the group
Currently participating in interventional clinical research treatment, or received other research drugs or used research devices within 4 weeks before the first administration
Active autoimmune diseases requiring systemic treatment (such as the use of disease relieving drugs, glucocorticoids or immunosuppressants) occurred within 2 years before the first administration
The study was receiving systemic glucocorticoid treatment (excluding local glucocorticoids by nasal spray, inhalation or other means) or any other form of immunosuppressive therapy within 7 days before the first administration; Note: It is allowed to use glucocorticoid with physiological dose (prednisone ≤ 10mg/day or equivalent)
Known history of allogeneic organ transplantation and allogeneic hematopoietic stem cell transplantation
According to the instructions of statins, there are contraindications to the use of statins
People who are allergic to any component of the drug
People with multiple factors affecting oral medicine (such as inability to swallow, gastrointestinal resection, significant digestive system diseases that may interfere with absorption, metabolism or excretion, such as chronic diarrhea or intestinal obstruction)