Management Strategy of 1L Lorlatinib With Hyperlipidemia in Stage IIIB-IV ALK Positive NSCLC

NCT07674524 | Not Yet Recruiting DMC

• 1 other identifier: B2026-159-01
• Study Type: observational
• Target: 160
• Locations: 1 country
• Sites: 1

Brief Summary

For Patients and Families Brief Title: Management of 1L Lorlatinib with Hyperlipidemia in ALK+ Advanced NSCLC What is this study about? This study is for people with ALK-positive non-small cell lung cancer (NSCLC) who are taking lorlatinib (Lorbrena®) as their first treatment and have developed high cholesterol (hyperlipidemia) as a side effect. Why is this study needed? Lorlatinib is a highly effective targeted therapy, but it frequently causes elevated cholesterol and triglycerides. There is currently no standard guideline on how to best manage this side effect. This study aims to find the best approach to control lipid levels while on lorlatinib treatment. What will happen in this study? The study has two parts:

• Part A (Observational) : About 100 participants. Doctors manage hyperlipidemia according to routine clinical practice. Researchers simply observe and record which lipid-lowering treatments are used and how well they work.
• Part B (Randomized Controlled Trial) : 60 participants with high-risk factors are randomly assigned to either:
• Intensive treatment: rosuvastatin + ezetimibe + evolocumab
• Standard treatment: rosuvastatin + ezetimibe What tests are involved?
• Blood tests for lipid levels at baseline, Weeks 4, 8, 20, and 24
• Routine CT or MRI scans for tumor assessment
• Some participants in Part B may have a non-invasive vascular ultrasound (FMD) test
• Total participation per patient: up to 7 months Is this study safe?
• ✅ Approved by the Ethics Committee of Sun Yat-sen University Cancer Center
• ✅ All drugs used (lorlatinib, statins, ezetimibe, evolocumab) are already approved and widely used
• ✅ An independent Data Monitoring Committee (DMC) monitors safety throughout the study
• ✅ Participants may withdraw at any time without affecting their regular care For Healthcare Providers Study Title: Management strategy of 1L Lorlatinib with Hyperlipidemia in Stage IIIB-IV ALK positive NSCLC: A multi-center prospective study in China Sponsor / Investigators: Sun Yat-sen University Cancer Center (PI: Prof. Zhang Li) Study Type:
• Part A: Observational, prospective, real-world cohort study
• Part B: Prospective, randomized controlled trial (RCT) Estimated Enrollment: 160 participants (Part A: \~100, Part B: 60) Study Duration: Approximately 4 years (anticipated completion: December 2029) Key Inclusion Criteria:
• Stage IIIB-IV ALK+ NSCLC (confirmed by IHC, FISH, PCR, NGS, or ctDNA)
• No prior systemic therapy for advanced/metastatic disease
• ECOG PS 0-2
• Age ≥ 18 years
• Hyperlipidemia (ULN ≤ TC \< 12.93 mmol/L, Grade 1-3) while on first-line lorlatinib
• At least one measurable lesion per RECIST v1.1
• Life expectancy ≥ 6 months Primary Endpoints:
• Part A: Describe real-world treatment patterns for hyperlipidemia management
• Part B: Percentage change in LDL-C from baseline to Week 12 Oversight:
• Independent Data Monitoring Committee (DMC)
• Trial Management Committee
• Ethics Committee of Sun Yat-sen University Cancer Center (Approval No. B2026-159-01) Participating Centers: 8 sites across China

Conditions

Hyperlipidemia; ALK-positive; Non-Small Cell Lung Cancer (NSCLC); ALK Gene Mutation

Keywords

Lorlatinib; ALK-positive NSCLC; Hyperlipidemia; Lipid management; Statin; Ezetimibe; Evolocumab; PCSK9 inhibitor; Real-world study; Randomized controlled trial; Prospective study; Endothelial function; FMD; Multi-center

Outcome Measures

Primary Outcomes (2)

• Percentage Change in LDL-C from Baseline to Week 12

  Description: The primary endpoint for Part B. The mean percentage change in low-density lipoprotein cholesterol (LDL-C) concentration from baseline to Week 12, compared between the intensive lipid-lowering group (rosuvastatin + ezetimibe + evolocumab) and the standard lipid-lowering group (rosuvastatin + ezetimibe).

  Baseline, Week 12

• Real-World Treatment Patterns for Hyperlipidemia Management

  Description: The primary endpoint for Part A. A descriptive analysis of the lipid-lowering management strategies used in routine clinical practice for ALK+ NSCLC patients developing hyperlipidemia on first-line lorlatinib, including treatment class selection (statins, ezetimibe, PCSK9 inhibitors), monotherapy versus combination therapy, timing of initiation, dose adjustments, and adherence to standard guideline recommendations.

  Baseline through Week 24 (measured at Baseline, Weeks 4, 8, 20, and 24)

Secondary Outcomes (1)

• Dynamic Changes in Lipid Profile Parameters over 24 Weeks

  Baseline, Weeks 4, 8, 12, 16, 20, 24 (Part B); Baseline, Weeks 4, 8, 20, 24 (Part A)

Other Outcomes (1)

• Change in Endothelial Function Measured by Brachial Artery Flow-Mediated Dilation (FMD)

  Baseline, Week 24

Study Arms (3)

Group/Cohort 1: Part A - Observational Cohort

* Description: No intervention assigned. Real-world lipid-lowering treatment patterns recorded per routine clinical practice. May include statins, ezetimibe, PCSK9 inhibitors, or combinations. * Participants: \~100 * Intervention: None (observational)

Drug: For Part A - Observational Cohort:

Group/Cohort 2: Part B - Intensive Lipid-Lowering Group

* Description: Intensive lipid-lowering therapy with rosuvastatin + ezetimibe + evolocumab (PCSK9 inhibitor) * Participants: 30 * Intervention: Rosuvastatin, Ezetimibe, Evolocumab

Drug: For Part B - Intensive Group

Group/Cohort 3: Part B - Standard Lipid-Lowering Group

Active Comparator ,Patients with high CVD risk randomized to receive standard combination therapy. Rosuvastatin + Ezetimibe .

Drug: Part B: Intensive Lipid-Lowering Group

Interventions

For Part A - Observational Cohort: DRUG

No intervention assigned (observational)

Group/Cohort 1: Part A - Observational Cohort

Part B: Intensive Lipid-Lowering Group DRUG

Rosuvastatin + Ezetimibe + Evolocumab

Group/Cohort 3: Part B - Standard Lipid-Lowering Group

For Part B - Intensive Group DRUG

Rosuvastatin + Ezetimibe

Group/Cohort 2: Part B - Intensive Lipid-Lowering Group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adult patients (≥ 18 years) with histologically or cytologically confirmed Stage IIIB-IV ALK-positive non-small cell lung cancer (NSCLC) who are receiving first-line lorlatinib and have developed hyperlipidemia (ULN ≤ TC \< 12.93 mmol/L, Grade 1-3). Participants are recruited from 8 study centers across China. For Part B specifically, patients must additionally have at least one prior major ASCVD event or baseline LDL-C ≥ 4.9 mmol/L with high-risk factors (premature CAD, familial hypercholesterolemia, CABG/PCI history, diabetes, hypertension, CKD stage 3-4, or current smoking).

You may qualify if:

• Diagnosis:
• Histologically or cytologically confirmed locally advanced \[defined as Stage IIIB/C per AJCC v7.0 and not amenable to multimodality treatment\] or metastatic (Stage IV) ALK-positive NSCLC; ALK status must be confirmed by Ventana ALK (D5F3) Companion Diagnostic (CDx) IHC (Ventana ULTRA or XT platform), FISH, PCR, next-generation sequencing (NGS), or circulating tumor DNA (ctDNA) testing;
• At least one measurable target lesion per RECIST v1.1, not previously irradiated; brain metastases are allowed;
• No prior systemic therapy for advanced (Stage IIIB/C not amenable to multimodality treatment) or metastatic (Stage IV) disease;
• Eastern Cooperative Oncology Group Performance Status (ECOG PS) 0, 1, or 2;
• Age ≥ 18 years;
• Hyperlipidemia during first-line lorlatinib treatment, with ULN ≤ TC \< 12.93 mmol/L (Grade 1-3);
• Life expectancy ≥ 6 months;
• Negative serum pregnancy test at screening for women of childbearing potential. Non-childbearing potential must meet at least one of the following:
• Postmenopausal status: regular menstrual cessation ≥ 12 months with no other pathological or physiological cause (serum FSH level may be used to confirm postmenopausal status, if applicable);
• Hysterectomy and/or bilateral oophorectomy;
• Medically confirmed ovarian failure; All other women (including those with tubal ligation) are considered of childbearing potential;
• Provide signed and dated informed consent from the patient (or legal representative), indicating full understanding of the study-related information.
• Patients with at least one prior major ASCVD event, or baseline LDL-C ≥ 4.9 mmol/L ± high-risk factors.
• Major ASCVD events:

You may not qualify if:

• Mixed squamous cell carcinoma, large cell carcinoma, or small cell lung cancer
• Prior systemic anticancer therapy for NSCLC, including chemotherapy, biologic therapy, immunotherapy, or any investigational drug
• Diagnosed genetic hypercholesterolemia (e.g., familial hypercholesterolemia, Part A only) or secondary dyslipidemia with a clear etiology (e.g., hypothyroidism, uncontrolled diabetes, nephrotic syndrome)
• Known allergy or history of severe adverse reaction to any study drug (including lorlatinib, statins, ezetimibe, or evolocumab)
• Presence of other severe diseases that may affect study compliance or outcome assessment, including advanced renal failure (eGFR \< 30 mL/min/1.73 m²) or severe hepatic impairment (Child-Pugh Class C)
• Pregnant or lactating women, or fertile individuals (male or female) unwilling to use effective contraception during the study
• Currently participating in another interventional clinical study that may interfere with this study; patients expected to be unable to complete follow-up or the first tumor efficacy assessment; patients with mental or psychological disorders who cannot provide informed consent or comply with study requirements (including treatment and follow-up)
• Subjects meeting any of the following criteria will not be included in this clinical study:
• Major surgery within 4 weeks prior to randomization; minor surgery (e.g., port placement) is permitted provided the incision is adequately healed
• Radiotherapy within 2 weeks prior to enrollment, including stereotactic or partial brain radiotherapy. Patients who complete whole brain radiotherapy within 4 weeks prior to randomization, or palliative radiotherapy outside the CNS within 48 hours prior to randomization, are also excluded
• Gastrointestinal abnormalities including: inability to take oral medication; need for parenteral nutrition; prior surgery affecting absorption (e.g., total gastrectomy, gastric banding); active inflammatory bowel disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer within the past 6 months; malabsorption syndrome
• Known or suspected severe hypersensitivity to the study drug or any of its excipients
• History of extensive, disseminated, or bilateral disease, or current Grade 3-4 interstitial fibrosis/interstitial lung disease, including but not limited to: pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, bronchiolitis obliterans, and pulmonary fibrosis
• Active malignancy within 3 years prior to randomization (excluding NSCLC, non-melanoma skin cancer, localized prostate cancer not requiring immediate treatment, or any carcinoma in situ)
• Concurrent use within 12 days prior to first lorlatinib dose of:

Sponsors & Collaborators

• Sun Yat-sen University: lead
• Pfizer: collaborator

Study Sites (1)

Sun Yat-sen University Cancer Center

Guangzhou, Guangdong, 510060, China

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Hyperlipidemias

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Dyslipidemias; Lipid Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Central Study Contacts

Li Zhang

CONTACT

020-87343458; Zhangli6@mail.sysu.edu.cn

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 24 Years
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor and Chief Physician

Study Record Dates

• First Submitted: June 2, 2026
• First Posted: June 29, 2026
• Study Start: August 1, 2026
• Primary Completion (Estimated): December 31, 2029
• Study Completion (Estimated): December 31, 2029
• Last Updated: June 29, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)