Anaplastic Lymphoma Kinase Gene TranslocationNCT04881916
Immune and Genomic Markers in ALK+ NSCLC
An observational study of Anaplastic Lymphoma Kinase Gene Translocation and Non-Small Cell Lung Cancer, run by Massachusetts General Hospital at 1 site in United States.
Trial 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) Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Anaplastic Lymphoma Kinase Gene Translocation, Non-Small Cell Lung Cancer
- How many people
- 100 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2021to 1 Jul 2027
- How long will I take part?
- 2 Years
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: Patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC)
Who may be able to join
- 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.
Show all 10Show fewer
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
United States1 site
Massachusetts General Hospital Cancer Center
Boston, Massachusetts, 02114
About this study
Official title: 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)
Read the 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.
- Keywords
- Anaplastic Lymphoma Kinase Gene Translocation, Non-Small Cell Lung Cancer, ALK
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| 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 being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 2 years
Secondary outcomes (5)
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.
Measured: 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.
Measured: 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
Measured: 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).
Measured: Up to 2 years
Tumor immunophenotype
Correlate the tumor immunophenotype such as PD-L1 expression level or tumor mutational burden (TMB) with clinical outcomes.
Measured: Up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 May 2021
- Study start1 Dec 2021
- Primary completion1 Jul 2027 (estimated)
- Study completion1 Jul 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Anaplastic Lymphoma Kinase Gene TranslocationStudies of the same condition, open and under way.
- More trials run by Massachusetts General HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Other
- Enrolment
- 100 participants (estimated)
- Target duration
- 2 Years
Sponsor and investigators
- Lead sponsor
- Massachusetts General Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- LUNGevity Foundation, Addario Lung Cancer Medical Institute
- Responsible party
- Principal investigator, Jessica Jiyeong Lin, M.D., Massachusetts General Hospital
- Investigators
- Jessica J Lin, MD, Principal investigator, Massachusetts General Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04881916
- Sponsor's protocol ID
- 20-237
- Status last verified
- Mar 2026
- First submitted
- 6 May 2021
- Last updated
- 30 Mar 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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.
Publications
Liang J, Waliany S, Do A, Peterson JL, Roberts P, Kennedy EA, Venanzi ES, Gainor JF, Lin JJ. ENIGMA+: a national, decentralized, remote consent study for clinical data and biospecimen collection in patients with ALK-positive advanced NSCLC. Oncologist. 2025 Sep 1;30(9):oyaf217. doi: 10.1093/oncolo/oyaf217.
PubMed 40674592
Study at a glance
From the registry record, last updated by the sponsor on 30 Mar 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Elucidating Novel Immune and Genomic Markers for ALK (ENIGMA+)
- ClinicalTrials.gov ID
- NCT04881916
- Acronym / sponsor ID
- 20-237
- Keywords
- Anaplastic Lymphoma Kinase Gene Translocation, Non-Small Cell Lung Cancer, ALK
- Study type
- Observational
- Recruitment status
- Active, not recruiting
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Massachusetts General HospitalUniversity, hospital or other
- Collaborators
- LUNGevity Foundation, Addario Lung Cancer Medical Institute
- Study start
- 1 Dec 2021 (actual)
- Primary completion
- 1 Jul 2027 (estimated)
- Study completion
- 1 Jul 2027 (estimated)
- First posted
- 11 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Observational model
- Cohort
- Time perspective
- Other
- Target follow-up
- 2 Years
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- Patients with advanced ALK-positive (ALK+) non-small cell lung cancer (NSCLC)
Key inclusion criteria (10 listed)
- 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.
Key exclusion criteria (5 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Registry Establishment
Time frame: 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.
5 secondary outcomes
Duration Of Therapy
Time frame: Up to 2 years
Overall survival (OS)
Time frame: Up to 2 years
ALK resistance mutations
Time frame: Up to 2 years
Genomic alterations
Time frame: Up to 2 years
Tumor immunophenotype
Time frame: Up to 2 years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Mar 2026.
- Derived from this study: PubMed 40674592Liang J, Waliany S, Do A, Peterson JL, Roberts P, Kennedy EA, Venanzi ES, Gainor JF, Lin JJ. ENIGMA+: a national, decentralized, remote consent study for clinical data and biospecimen collection in patients with ALK-positive advanced NSCLC. Oncologist. 2025 Sep 1;30(9):oyaf217. doi: 10.1093/oncolo/oyaf217.
- Individual participant dataSharing planned: Yes. 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.
Related trials for Anaplastic Lymphoma Kinase Gene Translocation
Active, not recruitingPhase 2
Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients
Lung Cancer, NSCLC
Active, not recruitingPhase 3
Crizotinib in Treating Patients With Stage IB-IIIA Non-small Cell Lung Cancer That Has Been Removed by Surgery and ALK Fusion Mutations (An ALCHEMIST Treatment Trial)
ALK Gene Rearrangement, ALK Gene Translocation
RecruitingPhase 4
Comparison of Standard Dose Alectinib to Alectinib in Adjusted Dose Based on Alectinib Bloodlevels
Drug Monitoring, Carcinoma, Non-Small-Cell Lung
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jessica J Lin, MD principal investigator
Massachusetts General Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Anaplastic Lymphoma Kinase Gene Translocation and Non-Small Cell Lung Cancer, run by Massachusetts General Hospital at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 10 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 30 Mar 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Registry Establishment (time frame: Up to 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04881916, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Mar 2026.