Advancing Brigatinib Properties in ALK+ NSCLC Patients by Deep Phenotyping

NCT04318938 | Active Not Recruiting Phase 2

• 1 other identifier: ABP
• Study Type: interventional
• Target: 118
• Locations: 1 country
• Sites: 26

Brief 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

Conditions

NSCLC

Keywords

ALK+ NSCLC; Resistance patterns; Molecular properties

Outcome Measures

Primary Outcomes (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

  68 months

Secondary Outcomes (11)

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

  68 months

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

  68 months

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

  68 months

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

  68 months

• Overall survival (OS)

  68 months

Other Outcomes (9)

• ALK variant analysis in tumor tissue

  68 months

• ALK variant analysis in blood samples

  68 months

• TP53 mutation status in tumor tissue

  68 months

Study Arms (2)

Standard Arm with any available ALK TKI

ACTIVE COMPARATOR

1. 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)

Drug: Tyrosine kinase inhibitor

Experimental Arm with Brigatinib

EXPERIMENTAL

1. 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

Drug: Brigatinib

Interventions

Brigatinib DRUG

Treatment with Brigatinib

Also known as: Study treatment

Experimental Arm with Brigatinib

Tyrosine kinase inhibitor DRUG

Treatment with any TKI

Also known as: Study treatment

Standard Arm with any available ALK TKI

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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
• 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

You may not qualify if:

• History or presence at baseline of pulmonary interstitial disease, drug-related pneumonitis, or radiation pneumonitis
• \*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.
• 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.

Sponsors & Collaborators

• Thoraxklinik-Heidelberg gGmbH: collaborator
• Takeda: collaborator
• Institut für Klinische Krebsforschung IKF GmbH at Krankenhaus Nordwest: lead

Study Sites (26)

HELIOS Klinikum Emil von Behring

Berlin, 14165, Germany

Location

Charité Berlin

Berlin, Germany

Location

Lungenklinik Köln - Merheim

Cologne, 51109, Germany

Location

Universitätsmedizin Essen

Essen, 45147, Germany

Location

Klinikum Esslingen

Esslingen am Neckar, 73730, Germany

Location

Krankenhaus Nordwest Frankfurt

Frankfurt am Main, 60488, Germany

Location

Universitätsklinikum Freiburg

Freiburg im Breisgau, Germany

Location

Niels-Stensen-Kliniken Georgsmarienhütte

Georgsmarienhütte, 49124, Germany

Location

Universitätsklinikum Gießen

Giessen, Germany

Location

Studiengesellschaft Hämato-Onkologie Hamburg

Hamburg, 20251, Germany

Location

Evangelisches Krankenhaus Hamm

Hamm, Germany

Location

KRH Klinikum Siloah Hannover

Hanover, 30459, Germany

Location

Medizinische Hochschule Hannover

Hanover, Germany

Location

Thoraxklinik am Universitätsklinikum Heidelberg

Heidelberg, 69126, Germany

Location

Lungenklinik Hemer

Hemer, Germany

Location

Universitätsklinikum Jena

Jena, 07740, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Klinik der LMU München - Innenstadt

München, Germany

Location

Universitätsklinikum Münster

Münster, Germany

Location

Klinikum Nürnberg

Nuremberg, 90419, Germany

Location

Pius Hospital Oldenburg

Oldenburg, 26121, Germany

Location

Universitätsklinikum Regensburg

Regensburg, 93053, Germany

Location

Klinik Schillerhöhe

Stuttgart, Germany

Location

Universitätsklinikum Ulm

Ulm, 89081, Germany

Location

Universitätsklinikum Würzburg

Würzburg, Germany

Location

Related Publications (1)

• 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.

  PMID: 34182952 DERIVED

MeSH Terms

Interventions

brigatinib; Pharmaceutical Preparations; Tyrosine Kinase Inhibitors

Intervention Hierarchy (Ancestors)

Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses

Study Officials

• Salah-Eddin Al-Batran, Prof.

  Institut für Klinische Krebsforschung IKF GmbH

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2020
• First Posted: March 24, 2020
• Study Start: March 30, 2020
• Primary Completion: April 30, 2026
• Study Completion: April 30, 2026
• Last Updated: March 2, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

DE (26)