Immune and Genomic Markers in ALK+ NSCLC

Elucidating Novel Immune and Genomic Markers for ALK (ENIGMA+)

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)

Study Overview

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

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 Type: Observational
• Enrollment (Estimated): 100

Contacts and Locations

• Study Contact: Name: Jessica J Lin, MD; Phone Number: 617-724-4000; Email: jjlin1@partners.org
• Study Contact Backup: Name: Allison M Harper, PharmD; Phone Number: 650-598-2857; Email: Clinicalops@alcmi.net

Study Locations

• United States
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital Cancer Center
      • Contact: Jessica J Lin, MD; Phone Number: 617-724-4000; Email: jjlin1@partners.org
      • Principal Investigator: Jessica J Lin, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC)

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Sample Collection; Participation In: Initial data completion: Telephone collection of information on disease, treatment and testing; Medical record collection: Collection of medical records regarding cancer, testing, and treatment history; Archival tissue collection: Collection of tumor from prior standard of care procedure; Saliva collection: Saliva collection with at home kit; Follow up data completion: Telephone collection of medical condition every 3-6 months up to 2 years.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Registry Establishment	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.	Up to 2 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Duration Of Therapy	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.	Up to 2 years
Overall survival (OS)	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.	Up to 2 years
ALK resistance mutations	Study the development of ALK resistance mutations in the TKI-resistant tumor specimen(s) as patients receive sequential ALK-targeted therapies	Up to 2 years
Genomic alterations	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).	Up to 2 years
Tumor immunophenotype	Correlate the tumor immunophenotype such as PD-L1 expression level or tumor mutational burden (TMB) with clinical outcomes.	Up to 2 years

Collaborators and Investigators

• Sponsor: Massachusetts General Hospital
• Collaborators: LUNGevity Foundation; Addario Lung Cancer Medical Institute
• Investigators: Principal Investigator: Jessica J Lin, MD, Massachusetts General Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2021
• Primary Completion (Estimated): December 1, 2025
• Study Completion (Estimated): December 1, 2025

Study Registration Dates

• First Submitted: May 6, 2021
• First Submitted That Met QC Criteria: May 6, 2021
• First Posted (Actual): May 11, 2021

Study Record Updates

• Last Update Posted (Actual): March 18, 2024
• Last Update Submitted That Met QC Criteria: March 15, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Non-Small Cell Lung Cancer; ALK; Anaplastic Lymphoma Kinase Gene Translocation
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung
• Other Study ID Numbers: 20-237

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The Dana-Farber / Harvard Cancer Center encourages and supports the responsible and ethical sharing of data from clinical trials. De-identified participant data from the final research dataset used in the published manuscript may only be shared under the terms of a Data Use Agreement. Requests may be directed to: [contact information for Sponsor Investigator or designee]. The protocol and statistical analysis plan will be made available on Clinicaltrials.gov only as required by federal regulation or as a condition of awards and agreements supporting the research.
• IPD Sharing Time Frame: Data can be shared no earlier than 1 year following the date of publication
• IPD Sharing Access Criteria: Contact the Partners Innovations team at http://www.partners.org/innovation
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No