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NSCLCPhase 2NCT04318938

Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping

A Phase 2 study testing Brigatinib and Tyrosine kinase inhibitor in people with NSCLC, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 26 sites in Germany.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a prospective, randomized, open-label, multicenter phase II study investigating the advancing Brigatinib properties in anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patients by deep phenotyping Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
NSCLC
What is being tested?
Brigatinib and Tyrosine kinase inhibitor
Could I receive a placebo?
No, everyone receives an active treatment
How many people
118 participants
Where
26 sitesGermany
Study dates
30 Mar 2020to 30 May 2026
Phase
Phase 2
Are there results?
None posted in the registry

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

Who may be able to join

  • Fully informed written consent and any locally-required authorization (EU Data Privacy Directive) given by the patient
  • Male or female ≥ 18 years of age NOTE: There are no data that indicate special gender distribution. Therefore, patients will be enrolled in the study gender-independently.
  • Histologically confirmed locally advanced (stage III) and not suitable for curative treatment, i.e. R0 operation or definitive chemo-/radiation, or metastatic (stage IV) ALK+ NSCLC NOTE: Documentation of ALK rearrangement by a positive result of any ALK assay approved in Germany [i.e. positivity for at least one of the three: immunohistochemistry (IHC), NGS, fluorescence in situ hybridisation (FISH)] must be available at baseline. Treatment can already be started based on a local ALK+ test result, but subsequent central testing of the baseline biopsy for molecular profiling, incl. determination of ALK variant and TP53 status, should be made possible for all patients.
  • No prior therapy for metastatic ALK+ NSCLC including therapy with ALK inhibitors. However, 1 or 2 cycles of chemotherapy, chemo-immunotherapy or immunotherapy as well as cerebral irradiation before inclusion in the study will be allowed.
  • At least 1 measurable (i.e., target) lesion per RECIST v1.1 or otherwise evaluable lesion (e.g. brain lesion with at least 5 mm of longest diameter if measured by high-resolution cMRT e.g. using 1 mm slices thickness and not planned for irradiation before the first response assessment).
  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
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  • Have adequate organ function, as determined by:
  • Total bilirubin ≤1.5x the upper limit of the normal range (ULN) (< 3x the ULN if Gilbert's disease is present)
  • Estimated glomerular filtration rate ≥30 mL/minute/1.73 m2 (calculated by Modification of Diet in Renal Disease (MDRD) or any other validated formula, see Appendix 13.4)
  • Alanine aminotransferase/aspartate aminotransferase ≤2.5x ULN NOTE: ≤5x ULN is acceptable if liver metastases are present.
  • Serum lipase or serum amylase ≤ 1.5x ULN
  • Platelet count ≥75x 109/L
  • Hemoglobin ≥9 g/dL
  • Absolute neutrophil count ≥1.5x 109/L
  • Willingness and ability to comply with scheduled visit and study procedures
  • Patient willing to participate in accompanying research program
  • Collection of current biopsy during screening must be feasible NOTE: For each patient a formalin-fixed, paraffin-embedded (FFPE) tumor tissue block must be available for biomarker evaluation. Excisional, incisional or core needle biopsies are appropriate, while fine needle aspirations are insufficient.
  • Women of childbearing potential (WOCBP) must have a negative pregnancy test within 7 days prior to randomization. Women must not be breastfeeding.
  • Female patients who:
  • are postmenopausal for at least 1 year before the screening visit, OR
  • are surgically sterile, OR
  • if they are of childbearing potential, agree to practice highly effective non-hormonal contraception from the time of signing the informed consent through at least 4 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
  • Male patients, even if surgically sterilized (i.e., status post-vasectomy), who:
  • agree to practice effective barrier contraception during the entire study treatment period and through at least 3 months after the last dose of study drug, OR
  • agree to completely abstain from heterosexual intercourse.

Who cannot join

  • History or presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis
  • Uncontrolled hypertension, defined as hypertension treated* with anti-hypertensive drugs AND blood pressure ≥ 160 mmHg (systolic) or ≥ 100 mmHg (diastolic) in repeated measurements. Untreated elevated blood pressure is not an exclusion criterion and should receive adequate anti-hypertensive adjustment.
  • Please notecase of treatment, at least 3 anti-hypertensive drugs should have been used with the intention to control hypertensive disease
  • Systemic treatment with strong cytochrome P-450 (CYP) 3A inhibitors, strong CYP3A inducers, or moderate CYP3A inducers or treatment with any investigational systemic anticancer agents, chemotherapy or radiation therapy (except for stereotactic radiosurgery or stereotactic radiation therapy or palliative radiotherapy) within 14 days of randomization
  • Treatment with antineoplastic monoclonal antibodies within 30 days of randomization
  • Major surgery within 30 days of randomization. Minor surgical procedures, such as catheter placement or minimally invasive biopsies, are allowed.
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  • Current symptomatic spinal cord compression as confirmed by radiographic imaging. Patients with leptomeningeal disease without symptomatic cord compression are allowed.
  • Significant or uncontrolled cardiovascular disease, defined as to the following:
  • If an acute myocardial infarction has ensued in the past 6 months, successful reperfusion has to be documented and the patient has to be free of symptoms
  • New York Heart Association Class III or IV heart failure (i.e. marked limitation in activity due to symptoms, even during less-than-ordinary activity, e.g. walking short distances (20-100 m). Comfortable only at rest) within 6 months prior to randomization
  • Any history of clinically significant ventricular arrhythmia, defined as ventricular tachycardia (VT), ventricular fibrillation (VF), or cardiac arrest
  • Cerebrovascular accident or transient ischemic attack within 6 months prior to first dose of study drug
  • Malabsorption syndrome or other gastrointestinal illness or condition that could affect oral absorption of the study drug
  • Active severe or uncontrolled chronic infection, including but not limited to, the requirement for intravenous antibiotics for longer than 2 weeks
  • History of HIV infection. Testing is not required in the absence of history.
  • Chronic hepatitis B (surface antigen-positive) or chronic active hepatitis C infection. Testing is not required in the absence of history.
  • Any serious medical condition or psychiatric illness that could, in the investigator's opinion, potentially compromise patient safety or interfere with the completion of treatment according to this protocol
  • Known or suspected hypersensitivity to brigatinib or other TKI or their excipients
  • Life-threatening illness unrelated to cancer
  • Involvement in the planning and/or conduct of the study (applies to both Takeda staff and/or staff of sponsor and study site)
  • Patient who might be dependent on the sponsor, site or the investigator
  • Patient who has been incarcerated or involuntarily institutionalized by court order or by the authorities [according to national Medicinal Products Act (Arzneimittelgesetz, AMG)]
  • Patients who are unable to consent because they do not understand the nature, significance and implications of the clinical trial and therefore cannot form a rational intention in the light of the facts [according to national AMG]
  • Legal incapacity or limited legal capacity
  • Females who are pregnant or breastfeeding
  • Patients who have symptomatic CNS metastases (parenchymal or leptomeningeal) at screening or asymptomatic disease requiring an increasing dose of corticosteroids to control symptoms within 7 days prior to randomization.
  • NOTE: If a patient has worsening neurological symptoms or signs due to CNS metastasis, the patient needs to complete local therapy and be neurologically stable (with no requirement for an increasing dose of corticosteroids or use of anticonvulsants) for 7 days prior to randomization.
  • Rare hereditary galactose intolerance, total lactase deficiency or glucose-galactose malabsorption

Trial locations and contacts

26 sites in 1 country.

26 sites in 1 country

Germany26 sites

  • HELIOS Klinikum Emil von Behring

    Berlin, 14165

  • Charité Berlin

    Berlin

  • Lungenklinik Köln - Merheim

    Cologne, 51109

  • Universitätsmedizin Essen

    Essen, 45147

  • Klinikum Esslingen

    Esslingen am Neckar, 73730

  • Krankenhaus Nordwest Frankfurt

    Frankfurt am Main, 60488

  • Universitätsklinikum Freiburg

    Freiburg im Breisgau

  • Niels-Stensen-Kliniken Georgsmarienhütte

    Georgsmarienhütte, 49124

  • Universitätsklinikum Gießen

    Giessen

  • Studiengesellschaft Hämato-Onkologie Hamburg

    Hamburg, 20251

  • Evangelisches Krankenhaus Hamm

    Hamm

  • KRH Klinikum Siloah Hannover

    Hanover, 30459

  • Medizinische Hochschule Hannover

    Hanover

  • Thoraxklinik am Universitätsklinikum Heidelberg

    Heidelberg, 69126

  • Lungenklinik Hemer

    Hemer

  • Universitätsklinikum Jena

    Jena, 07740

  • Universitätsklinikum Leipzig

    Leipzig, 04103

  • Universitätsmedizin Mainz

    Mainz, 55131

  • Klinik der LMU München - Innenstadt

    München

  • Universitätsklinikum Münster

    Münster

  • Klinikum Nürnberg

    Nuremberg, 90419

  • Pius Hospital Oldenburg

    Oldenburg, 26121

  • Universitätsklinikum Regensburg

    Regensburg, 93053

  • Klinik Schillerhöhe

    Stuttgart

  • Universitätsklinikum Ulm

    Ulm, 89081

  • Universitätsklinikum Würzburg

    Würzburg

Other trials in Germany

About this study

Official title: Advancing Brigatinib Properties in Anaplastic Lymphoma Kinase Positive Non-small Cell Lung Cancer (ALK+ NSCLC) Patients

This is a prospective, randomized, open-label, multicenter phase II study investigating the advancing Brigatinib properties in anaplastic lymphoma kinase positive non-small cell lung cancer (ALK+ NSCLC) patients by deep phenotyping

Read the detailed description

The aim of this study is to compare efficacy of brigatinib and other 2nd-generation ALK tyrosin kinase inhibitor (TKI) in 1st and 2nd line treatment and to explore resistance patterns according to treatment and molecular properties of the tumors

Conditions
NSCLC
Being tested
Brigatinib, Tyrosine kinase inhibitor
Keywords
ALK+ NSCLC, Resistance patterns, Molecular properties

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BrigatinibDrug

    Also called Study treatment

    Treatment with Brigatinib

  • Tyrosine kinase inhibitorDrug

    Also called Study treatment

    Treatment with any TKI

Study groups in NCT04318938
Study groupRoleWhat they receive
Standard Arm with any available ALK TKIActive comparator1. st line: Any approved 2nd-generation TKI according to investigator's choice 2. nd line: Any available ALK TKI according to investigator's choice (patients from the standard Arm A can be offered brigatinib in the 2nd line)
Receives: Drug: Tyrosine kinase inhibitor
Experimental Arm with BrigatinibExperimental1. st line: 90 mg brigatinib once daily p.o. for the first 7 days (lead-in) followed by 180 mg brigatinib once daily p.o. afterwards, starting with day 8 2. nd line: Any available ALK TKI according to investigator's choice
Receives: Drug: Brigatinib

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free survival (PFS) of 1st-line treatment according to RECIST v1.1

    Time from the first dosing date of any study medication to the date of the first objectively documented tumor progression or death due to any cause

    Measured: 68 months

Secondary outcomes (11)

  1. PFS of 2nd-line treatment according to RECIST v1.1

    Time from the first dosing date of any 2nd-line TKI to the date of the objectively documented tumor progression or death due to any cause

    Measured: 68 months

  2. TNT 1st line (TNT1, i.e. time-to-next treatment for the 1st line)

    Time from begin of 1st-line treatment until begin of 2nd-line treatment

    Measured: 68 months

  3. TNT 2nd line (TNT2, i.e. time-to-next treatment for the 2nd line

    Time from begin of 2nd line until begin of 3rd-line treatment

    Measured: 68 months

  4. TNT1/2 (time-to-next treatment for the 1st and 2nd line together)

    Time from begin of 1st-line treatment until begin of 3rd-line treatment

    Measured: 68 months

  5. Overall survival (OS)

    Time from treatment start in the 1st line to the date of death (due to any cause)

    Measured: 68 months

  6. Intracranial ORR (iORR)

    Percentage of participants with a best overall intracranial response (BOR) of intracranial complete response (CR) or intracranial partial response (PR). Best overall intracranial response (BOR) is defined as the best response designation, recorded between the date of first dose and the date of the initial objectively documented intracranial tumor progression per RECIST criteria or the date of subsequent therapy or death, whichever occurs first.

    Measured: 68 months

  7. Intracranial DOR (iDOR) according to RECIST v1.1

    Time from first documentation of intracranial CR or PR according to RECIST v1.1 (whichever is first recorded) until the first date that the intracranial progressive disease (PD) is objectively documented or until death (whichever occurs first

    Measured: 68 months

  8. Time to intracranial progression (TTiP)

    Time from start of 1st-line treatment until the occurrence of a new central nervous system (CNS) lesion or progression of pre-existing CNS lesions

    Measured: 68 months

  9. Safety (rate of adverse events)

    Type, incidence and severity of adverse events (AEs) and serious adverse events (SAEs)graded according to NCI CTCAE v5.0

    Measured: 68 months

  10. Quality of life (QoL) assessed by SF-12-questionnaire

    Patient reported outcome assessed by the validated SF-12-questionnaire

    Measured: 68 months

  11. Quality of life (QoL) assessed by EORTC-quality of life questionnaire (QLQ)-BN20-questionnaire

    Patient reported outcome assessed by the validated EORTC-QLQ-BN20-questionnaire

    Measured: 68 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Mar 2020
  2. Study start30 Mar 2020
  3. Primary completion30 May 2026
  4. Study completion30 May 2026

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
118 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04318938
Sponsor's protocol ID
ABP
Status last verified
Jun 2026
First submitted
18 Mar 2020
Last updated
23 Jun 2026
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No: No IPD will be shared

Publications

  • Christopoulos P, Bozorgmehr F, Bruckner L, Chung I, Krisam J, Schneider MA, Stenzinger A, Eickhoff R, Mueller DW, Thomas M. Brigatinib versus other second-generation ALK inhibitors as initial treatment of anaplastic lymphoma kinase positive non-small cell lung cancer with deep phenotyping: study protocol of the ABP trial. BMC Cancer. 2021 Jun 28;21(1):743. doi: 10.1186/s12885-021-08460-w.

    PubMed 34182952

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brigatinib and Tyrosine kinase inhibitor in people with NSCLC, run by Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest at 26 sites in Germany.

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 25 inclusion and 28 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: finished, as of the sponsor's last update on 23 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 26 sites in Germany. 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.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Progression-free survival (PFS) of 1st-line treatment according to RECIST v1.1 (time frame: 68 months). 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 NCT04318938, 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 23 Jun 2026.

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