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

Statin Combined With PD-1/PD-L1 Inhibitors in Treating NSCLC

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: immunotherapy

Detailed 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.

• Study Type: Observational
• Enrollment (Estimated): 250

Contacts and Locations

• Study Contact: Name: Kai Wang, PhD; Phone Number: 13957158572; Email: doctorhuxi@163.com
• Study Contact Backup: Name: Jiangnan Zhao, PhD; Phone Number: 18267098035; Email: zjn911016@126.com

Study Locations

• China
  • Zhejiang
    • Yiwu, Zhejiang, China, 310000
      • The Fourth Affiliated Hospital of Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

According to indications of statins, the enrolled people are divided into statin group and non-statin group.

Description

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)

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Standard programme group; Standard programme group, immunotherapy alone
controlled programme group; controlled programme group, statin combined with immunotherapy	Drug: immunotherapy; statin combined with immunotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
objective response rate	Refers to the proportion of patients whose tumor shrinkage reaches a certain amount and remains for a certain period of time, including CR + PR cases	three years
progression-free survival	Patients with oncological diseases have a period of time from the start of treatment to the observation of disease progression or death due to any cause	three years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
overall survival	The time from randomization to death due to any cause. For subjects who have been lost to follow-up before death, the time of the last follow-up is usually calculated as the time of death.	five years

Collaborators and Investigators

• Sponsor: The Fourth Affiliated Hospital of Zhejiang University School of Medicine
• Collaborators: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Kai Wang, PhD, The Fourth Affiliated Hospital of Zhejiang University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2027

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: November 24, 2022
• First Posted (Actual): December 5, 2022

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: March 7, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Physiological Effects of Drugs; Immunologic Factors; Immunomodulating Agents
• Other Study ID Numbers: K2022145

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No