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

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

Trial statusNot yet recruiting

Trial phaseNot listed

Trial typeObservational

Biological sexAll

Age18+

SponsorSun Yat-sen University

About this trial

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

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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;

Disqualifiers

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)

Trial 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).

Trial design

Design model

Cohort

Time perspective

Prospective

Treatments tested in this trial

For Part A - Observational Cohort:
Drug
No intervention assigned (observational)
Part B: Intensive Lipid-Lowering Group
Drug
Rosuvastatin + Ezetimibe + Evolocumab
For Part B - Intensive Group
Drug
Rosuvastatin + Ezetimibe

Treatment groups

160 Participants

are divided into 3 treatment groups

Group A: Group/Cohort 1: Part A - Observational Cohort1 intervention

Group B: Group/Cohort 2: Part B - Intensive Lipid-Lowering Group1 intervention

Group C: Group/Cohort 3: Part B - Standard Lipid-Lowering Group1 intervention

Trial outcomes

Primary outcomes

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).

Time frame

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.

Time frame

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

Secondary outcomes

Dynamic Changes in Lipid Profile Parameters over 24 Weeks

Description: Changes in total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) concentrations over the 24-week study period.

Time frame

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

Other outcomes

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

Description: Change in brachial artery flow-mediated dilation (FMD) from baseline to within 24 weeks of treatment, as an exploratory assessment of endothelial function changes associated with lorlatinib-related dyslipidemia and lipid-lowering interventions. Only performed in Part B, on a voluntary basis and where the study center has the required equipment and qualified personnel.

Time frame

Baseline, Week 24

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Sun Yat-sen University

Lead sponsor

Pfizer

Collaborator

Source ClinicalTrials.gov

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