marked.bio

ALK TKI (2nd generation) · small molecule

brigatinib

6 active trials across 2 of our biomarkers, targeting ALK. 3 active approvals for a biomarker on marked.bio.

Also known as AP26113, Alunbrig.

Counts only trials that select patients by one of the biomarkers on marked.bio, not every trial of this drug.

Approvals and pivotal results

Biomarker-selected approvals in the United States and the European Union, with the pivotal trial's results and side effects where we have them. Results from different trials are not directly comparable.

TherapyBiomarkerTumourUnited StatesEuropean Union
brigatinib
FDA, 2017
metastatic, ALK-positive AA 28/04/2017 (after crizotinib), converted to regular approval 22/05/2020 with first-line use. Current DailyMed label not retrieved. Source
EU (EMA), 2018
ALK-positive advanced NSCLC previously treated with crizotinib MA 22/11/2018. First-line indication added 01/04/2020 (II/0003), now its own row. Source
EU (EMA), 2020
ALK-positive advanced NSCLC not previously treated with an ALK inhibitor II/0003, EC decision 01/04/2020. Source
Alunbrig 		ALK fusion NSCLC Approved 2017 Approved 2018

In the US label

ALTA-1L vs crizotinib, 137 vs 138 patients
PFS 24.0 months vs 11.0 months, HR 0.49 (0.35-0.68)Response 74% vs 62%

Serious side effects 33%Stopped for side effects 13%Fatal 2.9%

Trial details and side effects
Patients
ALK-positive NSCLC not previously treated with an ALK inhibitor (NCT02737501)
Most common side effects
diarrhoea 53%, rash 40%, cough 35%, fatigue 32%, hypertension 32%, nausea 30% (136 patients)
Later trial
Brain metastases: response in the brain 78% vs 26% (18 vs 23 patients with measurable lesions).
Notes
US label rev. 10/2024.
Source
US label

In the EU product information

ALTA (180 mg arm) single-arm, 110 patients
Response 56% (independent review) (47-66)Lasting 15.7 months

Trial details and side effects
Patients
ALK-positive NSCLC after crizotinib (NCT02094573)
Notes
EU SmPC section 5.1 (ALTA 180 mg arm, later data cut). Median PFS 16.7 months.
Source
EU product information

In the EU product information

ALTA-1L vs crizotinib, 137 vs 138 patients
PFS 24.0 months vs 11.1 months, HR 0.48 (0.35-0.66)Response 75% vs 62%OS HR 0.81 (0.53-1.22), not significant

Trial details and side effects
Patients
ALK-positive NSCLC not previously treated with an ALK inhibitor (NCT02737501)
Most common side effects
diarrhoea 53%, rash 40%, cough 35%, fatigue 32%, hypertension 32%, nausea 30% (136 patients)
Later trial
Brain metastases: response in the brain 78% vs 26% (18 vs 23 patients with measurable lesions).
Notes
EU SmPC section 5.1 (ALTA-1L). Side effects from the US label.
Source
EU product information

Biomarkers

BiomarkerActive trialsAll trialsFurthest active phase
ALK fusion 6 24 Phase 2
ROS1 fusion 0 4 –

Trials

6 of 25 trials shown

  1. Study of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)

    Active, not recruiting Phase 2 Intergroupe Francophone de Cancerologie Thoracique Started 2022Primary completion 2025-09 NCT05200481

    brigatinib FDA EUcarboplatinpemetrexed

    …udy of Safety and Efficacy of Brigatinib Plus Chemotherapy or Brigatinib Only in Advanced ALK-Positive Lung Cancer (MASTERPROTOCOL ALK)

    ALK fusionNon Small Cell Lung Cancer, ALK Gene Mutation

  2. Brigatinib in Pediatric and Young Adult Patients With ALK+ ALCL, IMT or Other Solid Tumors

    Recruiting Phase 1/2 Princess Maxima Center for Pediatric Oncology Started 2022Primary completion 2033-12 NCT04925609

    brigatinib FDA EU

    Patients are required to provide prior results showing an activating ALK aberration in the tumor per local laboratory results, and material needs to be available for central…

    ALK fusionAnaplastic Large Cell Lymphoma, ALK-Positive, Inflammatory Myofibroblastic Tumor, Other Solid Tumor

  3. ALK Tyrosine Kinase Inhibitors in ALK-rearranged Advanced Squamous Cell Carcinoma

    Recruiting Phase 2 Hunan Province Tumor Hospital Started 2021Primary completion 2026-06 NCT05014464

    crizotinib FDA EUalectinib FDA EUbrigatinib FDA EUlorlatinib FDA EUpemetrexedcarboplatinpaclitaxel

    ALK fusion positive evaluated by IHC (ventana), NGS or FISH.

    ALK fusionStatus may be outdated, last updated 2024-09-20Non-small Cell Lung Cancer

  4. Clinical Utility of Liquid Biopsy in Brigatinib ALK+ Patients

    Active, not recruiting Phase 2 Fundación GECP Started 2020Primary completion 2026-11 NCT04223596

    brigatinib FDA EU

    …nal Association for the Study of Lung Cancer Staging Manual in Thoracic Oncology, that is ALK+

    ALK fusionLung Cancer, NSCLC, NSCLC Stage IIIB, NSCLC Stage IV

  5. Brigatinib and Bevacizumab for the Treatment of ALK-Rearranged Locally Advanced, Metastatic, or Recurrent NSCLC

    Active, not recruiting Phase 1 City of Hope Medical Center Started 2020Primary completion 2027-03 NCT04227028

    bevacizumabbrigatinib FDA EU

    …ither primary or metastatic site) diagnosis of locally advanced, recurrent, or metastatic ALK rearranged non-small cell lung cancer (NSCLC)

    ALK fusionLocally Advanced Lung Non-Small Cell Carcinoma, Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8

  6. Local Consolidative Therapy and Brigatinib in Treating Patients With Stage IV or Recurrent Non-small Cell Lung Cancer

    Active, not recruiting Phase 1 M.D. Anderson Cancer Center Started 2018Primary completion 2026-01 NCT03707938

    brigatinib FDA EU

    …l of Local Consolidative Therapy (LCT) With Brigatinib in Tyrosine Kinase Inhibitor-Naive ALK-Rearranged Advanced NSCLC

    ALK fusionAdvanced Lung Carcinoma, ALK Gene Rearrangement, Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma