Immune and Genomic Markers in ALK+ NSCLC

Recruiting

• Conditions: Anaplastic Lymphoma Kinase Gene Translocation; Non-Small Cell Lung Cancer

• Registration Number: NCT04881916
• Lead Sponsor: Massachusetts General Hospital

Brief Summary

The purpose of this research study is to obtain and study clinical history, and tissue and saliva specimens if available from participants with Anaplastic Lymphoma Kinase-ALK+ Non-Small Lung Cancer(NSCLC)

Detailed Description

The purpose of this study is to establish a registry of clinical data and tumor specimens of patients with advanced ALK+ non-small lung cancer (NSCLC) (defined as NSCLC harboring an ALK gene rearrangement). This will allow in-depth, comprehensive genomic and immunophenotypic analyses of ALK+ tumors. Together with the clinical data, these biologic specimens will enable the conduct of basic and translational research to identify genomic and immunologic markers associated with clinical outcomes for ALK+ patients.

Study Timeline

• Study First Submitted: 2021-05-06
• Study First Submitted QC: 2021-05-06
• Study First Posted: 2021-05-11
• Study Start: 2021-12-01
• Status Verified: 2024-03
• Last Update Submitted: 2024-03-15
• Last Update Posted: 2024-03-18
• Primary Completion: 2025-12-01
• Study Completion: 2025-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

Cohort 1 - Alive Individuals

• Men or women 18 years of age or the age of majority for their residential state of the United States, or older, at the time of consent.
• Histologically or cytologically confirmed advanced stage IIIB-IIIC not amenable to curative approach multi-modality (e.g., chemoradiation and/or surgery) treatment, or stage IV non-small cell lung cancer (NSCLC)
• Demonstration of having advanced ALK+ NSCLC, as assessed by fluorescence in situ hybridization (FISH), immunohistochemistry (IHC), next-generation sequencing (NGS) or circulating tumor DNA analysis (ctDNA). For ALK FISH, fusions must have been detected in at least 15% of tumor cells.
• Willingness to provide clinical and medical information to the study team as required.
• Willingness to provide archival tumor tissue, if available. Patients may enroll even if no tumor tissue is available.
• Ability to read, write and communicate in English.
• Ability to sign a web-based informed consent form.

Cohort 2 - Deceased Individuals

• Deceased individuals diagnosed with advanced ALK+ lung cancer at age 18 years or older may be studied on a case by case basis. Inclusion will require availability of adequate archived tissue and release of tissue and records by next of kin, if available.

Exclusion Criteria

• Participants who are unwilling to provide informed consent.
• Participants who are younger than 18 years of age.
• Participants who are unable to comply with the study procedures.
• Known existence of an uncontrolled intercurrent illness including, but not limited to, psychiatric illness or social situations that would impair compliance with study requirements.
• Participants who have previously enrolled to the study.

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Registry Establishment	Up to 2 years	Establish a registry of clinical data and tumor specimens from goal of 100 patients with advanced ALK+ NSCLC (defined as NSCLC harboring an ALK gene rearrangement), for characterization of the immunophenotype and genomic landscape of ALK+ NSCLC.

Secondary Outcome Measures

Name	Time	Method
Overall survival (OS)	Up to 2 years	To determine the overall survival (OS) of ALK+ NSCLC patients treated with sequential ALK TKIs and/or ICIs. OS for patient will be estimated using the Kaplan-Meier method, and 95% confidence intervals (CIs) will be calculated using the log-log transformation Overall survival (OS) will be calculated as the time from the first dose of the drug of interest to death due to any cause.
Duration Of Therapy	Up to 2 years	To determine the clinical outcomes (durations of therapy) on ALK Tyrosine kinase inhibitor-TKI(s) and/or immune checkpoint inhibitor-ICI(s) of ALK+ NSCLC patients. Duration of therapy will be estimated using the Kaplan-Meier method, and 95% confidence intervals (CIs) will be calculated using the log-log transformation.
ALK resistance mutations	Up to 2 years	Study the development of ALK resistance mutations in the TKI-resistant tumor specimen(s) as patients receive sequential ALK-targeted therapies
Tumor immunophenotype	Up to 2 years	Correlate the tumor immunophenotype such as PD-L1 expression level or tumor mutational burden (TMB) with clinical outcomes.
Genomic alterations	Up to 2 years	To determine the presence of genomic alterations such as single nucleotide variants, insertions or deletions, or copy number alterations in other cancer-related genes in the post-TKI tumor specimen(s).

Trial Locations

Locations (1)

Massachusetts General Hospital Cancer Center; 🇺🇸 Boston, Massachusetts, United States