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Non Small Cell Lung CancerPhase 2MP-ALKNCT05200481

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

A Phase 2 study testing Brigatinib 180 MG, Carboplatin and Pemetrexed in people with Non Small Cell Lung Cancer and ALK Gene Mutation, run by Intergroupe Francophone de Cancerologie Thoracique at 29 sites in France.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
Search all trials

Trial summary

This is a phase II randomized, open-labelled, non-comparative multicenter study in which ALK+ NSCLC patients who are naïve of treatment for advanced disease will be randomized to receive brigatinib monotherapy (Arm A) or brigatinib and carboplatin-pemetrexed therapy (Arm B). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer, ALK Gene Mutation
What is being tested?
Brigatinib 180 MG, Carboplatin and Pemetrexed
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
29 sitesFrance
Study dates
18 May 2022to Oct 2028
Phase
Phase 2
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

Who may be able to join

  • Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. Subjects must be willing and able to comply with scheduled visits, treatment schedule, and laboratory testing.
  • Patients diagnosed with histologically or cytologically confirmed locally advanced not eligible to a local treatment or metastatic NSCLC (Stage IIIB, IIIC or IV accordingly to 8th classification TNM, UICC 2015).
  • Patients are eligible for trial entry on the basis of locally determined ALK testing. ALK Immunohistochemistry (IHC) assay (3+ only), DNA-based or RNA-based next generation sequencing (NGS) assay, nCounter Nanostring assay or ALK FISH performed locally are accepted ALK testing assays. If ALK rearrangement diagnostic is performed using IHC and the result is + or 2+, a confirmation with a second method performed locally (DNA-based or RNA-based NGS assay, nCounter Nanostring assay or ALK FISH performed) is required.
  • All Patients must have at least one measurable target lesion according to RECIST v1.1 per investigator assessment. The radiological assessment has to be done within the timelines indicated.
  • Patients with asymptomatic and neurologically stable CNS metastases (including patients controlled with less than 10mg/day of methylprednisolone within the last week prior to study entry) will be eligible.
  • Tumor Sample Requirement: sufficient tumor tissue for central analysis should be available (tumor block or a minimum of 10 unstained slides of 4 µm of analyzable tissue).
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  • Age ≥18 years.
  • Life expectancy of at least 12 weeks, in the opinion of the Investigator.
  • Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
  • Adequate Bone Marrow Function, including: Absolute Neutrophil Count (ANC) ≥1.5 x 109/L; Platelets ≥100 x 109/L; Hemoglobin ≥9 g/dL.
  • Adequate Pancreatic Function, including: Serum lipase ≤3.0 ULN.
  • Adequate Renal Function, including: Estimated creatinine clearance ≥45 mL/min as calculated using the standard method of the institution.
  • Adequate Liver Function, including: Total serum bilirubin ≤1.5 x ULN (<3.0 × ULN for patients with Gilbert syndrome); Aspartate Aminotransferase (AST) and Alanine Aminotransferase (ALT) ≤2.5 x ULN; ≤5.0 x ULN if there is liver metastases involvement.
  • Participants must have recovered from toxicities related to prior anticancer therapy to CTCAE Grade ≤ 1.
  • Participants must have recovered from effects of any major surgery, or significant traumatic injury, at least 35 days before the first dose of treatment.
  • Have normal QT interval on screening ECG evaluation, defined as QT interval corrected (QTc) of ≤450 milliseconds (msec) in males or ≤470 msec in females.
  • 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 2 effective methods of contraception, at the same time, one of them being nonhormonal, from the time of signing the informed consent through 6 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 6 months after the last dose of study drug, or agree to completely abstain from heterosexual intercourse.
  • Willingness and ability to comply with the study scheduled visits, treatment plans, laboratory tests and other procedure.
  • Participant has national health insurance coverage.

Who cannot join

  • Previously received an investigational antineoplastic agent for NSCLC.
  • Previously received any prior TKI, including ALK-targeted TKIs.
  • Known molecular co-alteration i.e. activating EGFR/BRAF/KRAS/MET mutation and ROS1/RET/NTRK fusion.
  • Previously received neo-adjuvant or adjuvant systemic chemotherapy or consolidation immunotherapy if completion of (neo) adjuvant/consolidation therapy occurred <12 months prior to randomization.
  • Patients who have leptomeningeal disease (LM) or carcinomatous meningitis (CM) according to MRI data and/or in case of documented cerebral spinal fluid (CSF) positive cytology.
  • Spinal cord compression.
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  • Patients with symptomatic or neurologically instable CNS metastases.
  • Major surgery within 30 days of study entry. Minor surgical procedures (e.g., port insertion, mediastinoscopy, surgical procedure for re-sampling) are not excluded, but sufficient time at investigator discretion should have passed for wound healing.
  • Radiation therapy within 2 weeks of study entry. Stereotactic or small field brain irradiation must have completed at least 2 weeks prior to study entry. Whole brain radiation must have completed at least 4 weeks prior to study entry.
  • Active and clinically significant bacterial, fungal, or viral infection including hepatitis B (HBV), hepatitis C (HCV), known human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS)-related illness.
  • Have significant, uncontrolled, or active cardiovascular disease, specifically including, but not restricted to: a) myocardial infarction within 6 months prior to the first dose of study drug; b) unstable angina within 6 months prior to the first dose of study drug; c) congestive heart failure within 6 months prior to the first dose of study drug; d) any history of ventricular arrhythmia; e) history of clinically significant atrial arrhythmia or clinically significant bradyarrhythmia as determined by the treating physician; f) cerebrovascular accident or transient ischemic attack within 6 months prior to the first dose of study drug.
  • Have uncontrolled hypertension. Patients with hypertension should be under treatment on study entry to control blood pressure.
  • History of grade 3 or 4 of interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis, pulmonary fibrosis and radiation pneumonitis.
  • Presence of interstitial fibrosis of any grade at baseline.
  • Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.
  • Evidence of active malignancy (other than current NSCLC, non-melanoma skin cancer, in situ cervical cancer, papillary thyroid cancer, DCIS of the breast or localized and presumed cured prostate cancer) within the last 3 years.
  • Active inflammatory gastrointestinal disease, malabsorption syndrome, chronic diarrhea, symptomatic diverticular disease or previous gastric resection or lap band.
  • Current use or anticipated need for food or drugs prohibited.
  • Patients presenting with abnormal Left Ventricular Ejection Fraction (LVEF) by echocardiogram or Multi-Gated Acquisition Scan (MUGA) according to institutional lower limits.
  • Have a known or suspected hypersensitivity to brigatinib, carboplatin or pemetrexed or their excipients.
  • Female patients who are both lactating and breastfeeding or have a positive serum pregnancy test during the screening period or a positive urine pregnancy test on Day 1 before first dose of study drug.
  • Received systemic treatment with strong cytochrome p-450 (cyp)3a inhibitors, strong cyp3a inducers, or moderate cyp3a inducers within 14 days before enrolment.

Trial locations and contacts

29 sites in 1 country.

29 sites in 1 country

France29 sites

  • CHU d'Angers

    Angers, 49033

  • CHU Besançon - Hôpital J. MINJOZ

    Besançon, 25030

  • Hôpital APHP Ambroise Paré

    Boulogne, 92104

  • Hospices Civils de Lyon - Hôpital Louis Pradel

    Bron, 69677

  • CHU Côte de Nacre

    Caen, 14000

  • Centre Jean Perrin

    Clermont-Ferrand, 63011

  • Centre Hospitalier Intercommunal de Créteil

    Créteil, 94000

  • Centre Georges-François Leclerc

    Dijon, 21079

  • Chu Grenoble

    Grenoble, 38043

  • Hôpital Calmette

    Lille, 59037

  • CHU Dupuytren

    Limoges, 87042

  • Centre Léon Bérard

    Lyon, 69373

  • Institut Paoli Calmettes

    Marseille, 13273

  • Hôpital Nord

    Marseille, 13915

  • Hôpital Arnaud de Villeneuve

    Montpellier, 34295

  • Centre Hospitalier

    Mulhouse, 68070

  • Hôpital Cochin

    Paris, 75014

  • Hôpital BICHAT

    Paris, 75877

  • Hôpital TENON

    Paris, 75970

  • Hôpital Haut-Lévèque

    Pessac, 33604

  • CHU Rennes - Hôpital Pontchaillou

    Rennes, 35033

  • Hôpital Charles Nicolle

    Rouen, 76031

  • Institut de Cancérologie de l'Ouest - René Gauducheau

    Saint-Herblain, 44805

  • Centre Hospitalier

    Saint-Quentin, 02100

  • Nouvel Hôpital Civil - Hôpitaux Universitaires de Strasbourg

    Strasbourg, 67091

  • HIA Sainte-Anne

    Toulon, 83800

  • Hôpital Larrey (CHU)

    Toulouse, 31059

  • Centre Alexis Vautrin

    Vandœuvre-lès-Nancy, 54511

  • Centre Hospitalier de Villefranche-sur-Saône

    Villefranche-sur-Saône, 69655

Other trials in France

About this study

Official title: A Phase II Randomized, Open-Labelled, Multicenter Study of Safety & Efficacy of Combination Brigatinib and Carboplatin-Pemetrexed Therapy or Brigatinib Monotherapy as First-Line Treatment in Advanced ALK-Positive Non-Small Cell Lung Cancer

This is a phase II randomized, open-labelled, non-comparative multicenter study in which ALK+ NSCLC patients who are naïve of treatment for advanced disease will be randomized to receive brigatinib monotherapy (Arm A) or brigatinib and carboplatin-pemetrexed therapy (Arm B). An estimated 110 patients (55 in Arm A, 55 in Arm B) will be enrolled at approximately 30 centers. A safety phase will evaluate the safety of brigatinib with carboplatin and pemetrexed treatment combination (Arm B). The first twenty-six patients enrolled in Arm B will represent the population of the safety phase. Patients will be treated until they experience progressive disease, intolerable toxicity, or another discontinuation criterion is met. Continuation of brigatinib beyond progression is permitted, at the investigator's discretion, if there is evidence of continued clinical benefit. The null hypothesis is progression free survival at 12 months ≤ 69% for Arm B, which is considered not sufficiently clinically meaningful to warrant further study. The alternative hypothesis is that 86% or more of patients in Arm B would achieve progression free survival at 12 months.

Being tested
Brigatinib 180 MG, Carboplatin, Pemetrexed
Keywords
IFCT, NCSLC, brigatinib, chemotherapy
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.

  • Brigatinib 180 MGDrug

    Also called ALUNBRIG

    Patients will receive brigatinib orally at a dose of 90 mg QD for a 7 days lead-in period followed by 180 mg QD continuously, with or without food, in 28-day cycles until progression. Dose reductions are possible.

  • CarboplatinDrug

    Patients will receive pemetrexed 500 mg/m² followed by carboplatin to target AUC of 5 mg/mL/min both on Day 1 as IV infusion every 3 weeks for 4 infusions. The first infusion of carboplatin and pemetrexed will be administrated at day 8 of brigatinib treatment, at time of dose escalation from 90 mg QD to 180mg QD continuously.

  • PemetrexedDrug

    Patients will receive pemetrexed 500 mg/m² followed by carboplatin to target AUC of 5 mg/mL/min both on Day 1 as IV infusion every 3 weeks for 4 infusions. The first infusion of carboplatin and pemetrexed will be administrated at day 8 of brigatinib treatment, at time of dose escalation from 90 mg QD to 180mg QD continuously.

Study groups in NCT05200481
Study groupRoleWhat they receive
Brigatinib monotherapy Arm AOtherBrigatinib 180mg QD (1 x 180mg tablet) until progression
Receives: Drug: Brigatinib 180 MG
Brigatinib Carboplatin-Pemetrexed combination therapy Arm BExperimentalBrigatinib 180mg QD (1 x 180mg tablet) until progression + Carboplatin AUC of 5 mg/mL/min IV infusion every 3 weeks for 4 infusions + pemetrexed 500 mg/m² IV infusion every 3 weeks for 4 infusions
Receives: Drug: Brigatinib 180 MG; Drug: Carboplatin; Drug: Pemetrexed

What is being measured

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

  1. Progression Free Survival at 12 months, investigator assessment

    Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause), determined by investigator assessment.

    Measured: 12 months

Secondary outcomes (13)

  1. Progression Free Survival (PFS) at 12 months, independent review

    Time from enrollment to first observation of progression (RECIST1.1) or date of death (from any cause), determined by independent review.

    Measured: 12 months

  2. Overall Response Rate (ORR)

    Proportion of patients who have achieved a best overall response of complete response or partial response (RECIST1.1), determined by investigator assessment and by independent review.

    Measured: At progression, after an average of 2 years

  3. Incidence, nature, and severity of adverse events

    Graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0 (NCI CTCAE v5.0).

    Measured: From time of informed consent through treatment period and up to 30 days post last dose of study treatment (average of 2 years)

  4. Impact of ALK fusion detection in ctDNA on 12-months progression free survival

    Proportion of patients who achieved progression free survival (RECIST1.1) with ALK fusion detection in ctDNA baseline liquid biopsy, determined by investigator assessment and by independent review.

    Measured: 12 months

  5. Impact of ALK fusion detection in ctDNA on overall response rate

    Proportion of patients who have achieved a best overall response of complete response or partial response (RECIST1.1) with ALK fusion detection in ctDNA baseline liquid biopsy, determined by investigator assessment and by independent review.

    Measured: At progression, after an average of 2 years

  6. Intracranial overall response rate

    Proportion of patients who have achieved a best overall response of complete response or partial response of the baseline measurable and non-measurable CNS disease (RECIST1.1 + RANO), determined by investigator assessment and by independent review.

    Measured: At progression, after an average of 2 years

  7. Intracranial progression free survival at 12 months

    Proportion of patients achieving an objective response (CR or PR) of the baseline measurable and non-measurable CNS disease according to RECIST 1.1 and Revised Assessment in Neuro Oncology (RANO) criteria, determined by investigator assessment and by independent review.

    Measured: 12 months

  8. Time until definitive health related quality of life score deterioration

    The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30/QLQ-LC13 questionnaire will be used to determine time until definitive HRQoL score deterioration.

    Measured: From enrollment to score deterioration, a period of up to 2 years

  9. Duration of response (DOR)

    Time from the date of first documented response (CR or PR) to the earliest date of disease progression (RECIST1.1), determined by investigator assessment and by independent review.

    Measured: At progression, after an average of 2 years.

  10. Disease control rate (DCR)

    Proportion of patients who have achieved a confirmed best overall response of CR, PR or SD (RECIST v1.1), determined by investigator assessment and by independent review.

    Measured: At progression, after an average of 2 years.

  11. Overall survival (OS)

    Time between the date of randomization and death or last date of follow-up.

    Measured: At death or lost to follow up, up to 5 years after randomisation.

  12. Duration of intracranial response (CNS DOR)

    Time from the first occurrence of an objective response (CR or PR) of the baseline measurable and non-measurable CNS disease for at least 12 weeks, according to RECIST 1.1. and Revised Assessment in Neuro Oncology (RANO) criteria, determined by investigator assessment and independent review.

    Measured: At progression, after an average of 2 years.

  13. Intracranial disease control rate (CNS DCR)

    Proportion of patients achieving a response (CR, PR or SD) of the baseline measurable and non-measurable CNS disease according to RECIST 1.1 and Revised Assessment in Neuro Oncology (RANO) criteria, determined by investigator assessment and independent review.

    Measured: At progression, after an average of 2 years.

Timeline

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

  1. First posted20 Jan 2022
  2. Study start18 May 2022
  3. Primary completion1 Sep 2025
  4. Study completionOct 2028 (estimated)

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
Model description
Interventional, phase II, randomized, open-labelled, non-comparative multicenter study with two parallel arms
Masking
None (open label)
Enrolment
110 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05200481
Sponsor's protocol ID
IFCT-2101
Acronym
MP-ALK
Status last verified
Nov 2025
First submitted
7 Jan 2022
Last updated
17 Nov 2025
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Brigatinib 180 MG, Carboplatin and Pemetrexed in people with Non Small Cell Lung Cancer and ALK Gene Mutation, run by Intergroupe Francophone de Cancerologie Thoracique at 29 sites in France.

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 20 inclusion and 22 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 17 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 29 sites in France. 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?

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?

Progression Free Survival at 12 months, investigator assessment (time frame: 12 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 NCT05200481.

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 17 Nov 2025.

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