ALK Gene Mutation

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

This interventional study aims to determine the pharmacokinetics of orally administered alectinib with dose escalation from 300 mg to 600 mg twice daily in Mexican patients with advanced ALK-positive NSCLC. The main question it aims to answer is: what will be the peak plasma concentrations of alectinib following sequential dose escalation (300, 450, and 600 mg BID) over nine weeks of pharmacokinetic evaluation (phase I) in Mexican patients with advanced ALK-rearranged NSCLC? In phase I (on days 0, 21, and 42), oral alectinib will be administered twice per day (BID) to patients with ALK-positive NSCLC; starting with 300 mg BID in 21-day cycles and dose escalation in 150 mg increments until 600 mg BID. Blood samples will be taken before and after administration of each dose (on days 1, 22, and 43). The primary endopoints in phase I will be dose-limiting toxicity (DLT) and PK parameters (Cmax. maximum plasma concentration; Tmax: time to reach maximum concentration: AUC 1-12: area under plasma ocncentrations-time curve steady-state concentration). At the end of the last blood collection (at day 43), the evaluation of each cycle will be at 600 mg, and the participant will be discharged to continue their treatment on an outpatient basis. Phase one will finish on day 63 of the study. In phase II, the chosen BID dose based on the phase I portion will be administrated until disease progression, development of unacceptable side effects, or withdrawal of consent. The primary endpoint in phase 2 is the overall response rate (ORR) per RECIST V.1.1.

A comparison of baseline tumor characteristics in oncogene-driven cancers to tumor characteristics after early response to Tyrosine Kinase Inhibitor (TKI) targeted treatment will allow identification of early adaptive mechanisms of cell survival. This will facilitate targeting and termination of these survival/ resistance pathways before they develop with rational combinations of therapeutic agents to improve outcomes.

The purpose of this study is to assess the Treatment Strategies and Survival Outcome for Non-small Cell Lung Cancer With Oncogenic Mutation.

The scope of GALILEO project (Genomic ALteratIons and cLonal EvOlution in ALK+ NSCLC) is to explore the feasibility of genomic longitudinal evaluation for ALK+ NSCLC patients in Italian routine practice and provide a detailed overview of resistance mechanisms and clinical outcomes according to current standard treatments.

This is an open-label, multiple centers, two-arms phase II study to evaluate the safety and efficacy Pembrolizumab,Bevacizumab in combination with Chemotherapy could improve PFS in Alectinib Failed ALK-rearranged Advanced Lung Adenocarcinoma with Persistent 5'ALK. The eligible patients should have Stage IV Adenocarcinoma ALK-rearranged tested by NGS Perisitent with 5'ALK Failed from first line Alectinib. The patients should meet the physical requirements to receive Pembrolizumab, Bevacizumab with Chemotherapy. All the patients who meet these requirements will be enrolled in this study. The eligible patients will be treated with Pembrolizumab 200 mg intravenously (IV) plus Bevacizumab 15mg/kg+ Pemetrexed 500mg/m2+Carboplatin AUC=4 for up to 4 cycles followed by Pembrolizumab 200mg Q3W+ Bevacizumab 15mg/kg+Pemetrexed 500mg/m2 for up to 31cycles or until disease progression, intolerable toxicity, or physician or participant decision.

This study aims to evaluate the activity and safety of the combination of platinum-pemetrexed based chemotherapy plus Lorlatinib in ALK positive Non-Small Cell Lung Cancer (NSCLC) with exclusively extracranial disease progression on Lorlatinib. Platinum-pemetrexed based chemotherapy plus Lorlatinib will be administered for an induction phase of four cycles. Subsequently, patients with response or stability of disease at radiological assessment will start the maintenance phase with pemetrexed-Lorlatinib in 21-day cycles until progression, unacceptable toxicity, death, or withdrawal of consent.

The goal of this clinical trial is to learn evaluate the safety and efficacy of the addition of radiation therapy to all tumour lesions, to first line medical treatment with alectinib in non-small cell lung cancer harbouring ALK-rearrangements. The main aims of the trial are to evaluate: * if the treatment combination is safe * if the treatment combination can inhibit progression Participants who have responded to 1st line alectinib will be treated with consolidation radiation therapy to all remaining tumour lesions while continuing on alectinib until disease progression, unacceptable toxicity or another discontinuation criterion is met.