Resistance Mechanisms and Sequential Treatment Strategies Following First-Line Lorlatinib in ALK-Positive NSCLC

Resistance Mechanisms and Sequential Treatment Strategies Following First-Line Lorlatinib in ALK-Positive NSCLC: A Multi-center, Observational, Prospective Real-world Cohort Study (LORES)

This is a prospective, multicenter, non-interventional, single-arm, real-world study planned to be conducted in China, aimed at exploring the resistance mechanisms of first-line lorlatinib treatment in patients with ALK-positive locally advanced or metastatic NSCLC, as well as the efficacy and safety of sequential treatments following lorlatinib resistance in the real-world setting.

Study Overview

• Status: Not yet recruiting
• Conditions: ALK-Positive NSCLC
• Intervention / Treatment: Other: Non Interventional Study; Other: No intervention administered

• Study Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Li Zi ming; Phone Number: 18017321562; Email: liziming1980@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

adult patients with ALK-positive locally advanced or metastatic NSCLC

Description

Inclusion Criteria

1. Age: Patients aged 18 years or older;
2. Histologically or cytologically confirmed locally advanced or metastatic NSCLC
3. Documened ALK resrrangemen by approved test (eg.. FisH,IHC. .r NGS).
4. first-line loelaninab treatment fom Apr2023-Apr-2027.
5. Evidenoe of popression to first-line lorlztinib within 2 weekes.

Exclusion Criteria

1. Previous treatment with other ALK-TKIs: Patients who have previously received any ALK TKI other than lorlatinib;
2. Concomitant medications: Patients who have received any systemic anti-tumor treatment other than lorlatinib before enrollment.

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
mechanisms of resistance to first-line lorlatinib	Reslstance Assessment; Liquld Blops-Blood eIDNA NGS; Tissue Biopsy (If applicablo)-NGS mechanisms of resistance to first-line lorlatinib; Propression patternPriary ressstanceAcquined resistance; Moleculsr mechanisms of progression via ctDNA/organize NGS testing.; Difference between the mnechsnisins of primary and acquired resistance	24 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploring the sequential treatment strategies and their efficacy and safety after first-line progression with lorlatinib	rwTTD1： discontinuation of lorlatinib for any reason (including disease progression, death, severe adverse events, or patient choice); rwTTD2： progression on first-line lorlatinib to discontinuation of the first sequential anti-tumor treatment for any reason (including disease progression, death, severe adverse events, or patient withdrawal from the study); rwORR2: the overall proportion of patients who achieve complete response (CR) and partial response (PR); rwDCR2: the overall proportion of patients who achieve complete response (CR), partial response (PR), and stable disease (SD); rwPFS2: progression on first-line lorlatinib to disease progression or death from any cause or last confirmed survival 6、1-year/2-year-rwPFS2 rate: he proportion of patients who remain progression-free within 1 year/2 years 7、the overall proportion of patients who survive within 1 year/2 years 8、Exploration of the proportion and related reasons for dose adjustment	24 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
To determine the optimal sequential treatment strategies for different resistance mechanisms and the impact of these resistance mechanisms on patient outcomes in sequential treatment	Explore the impact of different resistance mechanisms on patient prognosis, and investigate the sequential treatment strategies (including treatment efficacy and safety, if data are available in clinical practice) for ALK-positive locally advanced or metastatic NSCLC patients after resistance to first-line lorlatinib.; Through comprehensive genomic analysis, explore which molecular pathological changes can provide guiding information for treatment after lorlatinib resistance, and identify which biomarkers can predict which patients are likely to benefit from specific treatments, thereby formulating individualized treatment plans to improve overall patient efficacy.	24 months

Collaborators and Investigators

• Sponsor: Shanghai Chest Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): April 20, 2025
• Primary Completion (Estimated): June 30, 2029
• Study Completion (Estimated): December 31, 2030

Study Registration Dates

• First Submitted: March 21, 2025
• First Submitted That Met QC Criteria: March 28, 2025
• First Posted (Actual): April 1, 2025

Study Record Updates

• Last Update Posted (Actual): April 11, 2025
• Last Update Submitted That Met QC Criteria: April 8, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: IS25052

Drug and device information, study documents

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