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Non Small Cell Lung CancerPhase 2AMAZE-lungNCT05601973

Amivantamab, Lazertinib and Bevacizumab in Patients With EGFR-mutant Advanced Non-small Cell Lung Cancer With Progression on Previous Third-generation EGFR-TKI

A Phase 2 study testing Amivantamab, Lazertinib and Zirabev in people with Non Small Cell Lung Cancer, run by ETOP IBCSG Partners Foundation at 18 sites in 6 countries.

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

AMAZE-lung is a multicenter single-arm phase II trial. The protocol treatment consists of amivantamab, lazertinib and bevacizumab (Zirabev®), given in a three-weekly regimen. The primary objective of the trial is to assess the efficacy of amivantamab and bevacizumab added to continued treatment with the… Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Non Small Cell Lung Cancer
What is being tested?
Amivantamab, Lazertinib and Zirabev
Could I receive a placebo?
No, everyone receives an active treatment
How many people
60 participants
Where
18 sitesin 6 countries
Study dates
27 Mar 2023to 30 Sep 2026
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

  • Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to radical therapy) or stage IV according to 8th TNM classification.
  • Presence of a sensitising EGFR-mutation (only patients with exon 19 deletion and/or L858R are eligible) and documentation of T790M status, tested locally by an accredited laboratory.
  • Radiologically confirmed disease progression on previous treatment with osimertinib or lazertinib.Treatment with osimertinib must have been stopped at least 8 days before enrolment.
  • Achieved objective clinical benefit from osimertinib or lazertinib treatment (e.g., documented PR/ CR or SD for ≥6 months while on osimertinib or lazertinib treatment).
  • Measurable disease as defined according to RECIST v1.1.
  • Age ≥18 years.
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  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
  • Life expectancy ≥12 weeks.
  • Adequate haematological function:
  • Haemoglobin ≥100 g/L,
  • Absolute neutrophil count (ANC) ≥1.5× 109/L,
  • Platelet count ≥75× 109/L.
  • Adequate renal function:
  • Serum creatinine <1.5× ULN and calculated (Cockcroft-Gault formula) or measured creatinine clearance >45 mL/min.
  • Adequate liver function:
  • ALT and AST ≤3× ULN. If the patient has liver metastases, ALT and AST must be ≤5× ULN.
  • Total bilirubin ≤1.5× ULN. Patients with Gilbert's syndrome are eligible if conjugated bilirubin is within normal limits.
  • Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative pregnancy test (b-human chorionic gonadotropin [b-hCG]) within 5 weeks before enrolment and within 3 days before the first dose of protocol treatment. Women of childbearing potential must use highly effective contraceptive methods.
  • Written IC for trial participation must be signed and dated by the patient and the investigator prior to any trial-related intervention.

Who cannot join

  • Patients with known small cell lung carcinoma (SCLC) transformation.
  • Patients with symptomatic brain metastases. Patients with asymptomatic or previously treated and stable brain metastases may participate in this study. Patients who have received definitive radiotherapy or surgery for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at ≥2 weeks before enrolment are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (≤10 mg/day prednisone or equivalent) for at least 2 weeks prior to enrolment.
  • Patients with an active or past medical history of leptomeningeal disease.
  • Patients with untreated spinal cord compression. Patients who have been definitively treated with surgery or radiotherapy and have a stable neurological status for ≥2 weeks prior to enrolment are eligible provided they are off corticosteroid treatment or are receiving low-dose corticosteroid treatment ≤10 mg/day prednisone or equivalent.
  • Patients with unresolved adverse events (other than alopecia) from prior anticancer therapy that have not resolved to grade ≤1 or baseline.
  • Patients with positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) test.
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  • Patients with positive hepatitis C antibody (anti-HCV) test.
  • Patients with other clinically active infectious liver disease.
  • Patients who are known positive for HIV, with one or more of the following:
  • Receiving antiretroviral therapy (ART) that may interfere with study treatment
  • CD4 count <350 at screening.
  • AIDS-defining opportunistic infection within 6 months before enrolment.
  • Not agreeing to start ART and be on ART >4 weeks plus having HIV viral load <400 copies/mL at end of 4-week period (to ensure ART is tolerated and HIV is under control).
  • Patients with active cardiovascular disease including, but not limited to:
  • Medical history of deep vein thrombosis or pulmonary embolism within 1 month prior to enrolment or any of the following within 6 months prior to enrolment: Myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome.
  • Prolonged corrected QTcF >470 msec, clinically-significant cardiac arrhythmia (e.g., atrial fibrillation with uncontrolled rate) or abnormalities in conduction or morphologiy of electrocardiogram (ECG) (e.g., complete left bundle branch block, third- or second-degree heart block, PR interval >250 msec), or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator).
  • Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as, hypokalemia, congenital long QT syndrome, family history of long QT syndrome, or unexplained sudden death under 40 years in first degree relatives or any concomitant medications known to prolong QT interval or induce TdP.
  • Uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg.
  • Congestive heart failure (CHF), defined as New York Heart Association (NYHA) class III-IV or hospitalisation for CHF (any NYHA class) within 6 months before enrolment.
  • An active or past medical history of pericarditis, pericardial effusion that is clinically unstable, or myocarditis.
  • Pericardial effusion considered due to the disease under study is permitted if clinically stable at screening.
  • Baseline LVEF either <50% or below the lower limit of normal (LLN) per institutional guidelines, as assessed by screening echocardiogram (ECHO) or multigated acquisition (MUGA) scan.
  • Patients with interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis.
  • Patients with a history of haemoptysis (≥2.5 mL of bright red blood per episode) within 1 month prior to enrolment.
  • Patients with evidence of bleeding diathesis or coagulopathy (in the absence of therapeutic anticoagulation).
  • Patients with current or recent (within 10 days before enrolment) use of aspirin (>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and clostazol.
  • Patients with current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes that has not been stable for >2 weeks prior to enrolment.
  • The use of full-dose oral or parenteral anticoagulants is permitted as long as the INR or aPTT is within therapeutic limits (according to the medical standard of the enrolling institution) and the patient has been on a stable dose of anticoagulants for at least 2 weeks prior to enrolment.
  • Prophylactic anticoagulation for the patency of venous access devices is allowed, provided the activity of the agent results in an INR <1.5× ULN and aPTT is within normal limits within 14 days prior to enrolment.
  • Prophylactic use of low-molecular-weight heparin (i.e., enoxaparin 40 mg/day) is permitted.
  • Patients with serious, non-healing wound, active ulcer, or untreated bone fracture.
  • Patients who had a core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to enrolment.
  • Patients who had major surgery or significant traumatic injury within 28 days prior to enrolment.
  • Patients who had placement of a vascular access device within 2 days prior to prior to enrolment.
  • Patients with a history of abdominal or tracheoesophageal fistula or gastrointestinal perforation within 6 months prior to enrolment.
  • Patients with clinical signs of gastrointestinal obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding.
  • Patients with evidence of abdominal free air not explained by paracentesis or recent surgical procedure.
  • Patients with concurrent or prior malignancy other than the disease under study.
  • Some exceptions require consultation with the ETOP IBCSG Partners
  • Patients with uncontrolled illness, including but not limited to:
  • Uncontrolled diabetes.
  • Ongoing or active infection, or diagnosed or suspected viral infection.
  • Active bleeding diathesis.
  • Impaired oxygenation requiring continuous oxygen supplementation.
  • Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated drug, or previous significant bowel resection
  • Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements.
  • Any ophthalmologic condition that is clinically unstable.
  • History of hypersensitivity to either the drug substance or any excipients in amivantamab, lazertinib and/ or bevacizumab.
  • Prior chemotherapy for NSCLC.
  • Prior treatment with bevacizumab or another anti-angiogenic inhibitor.
  • Prior treatment with a MET/EGFR-targeting antibody.
  • Judgement by the investigator that the patient should not participate in the study if the patient is unlikely to comply with study procedures, restrictions and requirements.
  • Women who are pregnant or in the period of lactation.
  • Women of childbearing potential or men who are sexually active with a woman of childbearing potential, who are not willing to use at least one method of highly effective contraception while receiving protocol treatment and for at least 6 months after the last dose of protocol treatment.

Trial locations and contacts

18 sites in 6 countries.

18 sites in 6 countries

Spain8 sites

  • Hospital Universitario de A Coruña

    A Coruña

  • Hospital Universitario Alicante Dr Balmis ISABIAL

    Alicante

  • ICO Badalona

    Badalona

  • Vall d´Hebron University Hospital VHIO

    Barcelona

  • Hospital Universitario Basurto

    Bilbao

  • Catalan Institute of Oncology

    L'Hospitalet de Llobregat

  • Hospital Universitario Fundación Jiménez Díaz

    Madrid

  • Hospital clínico universitario de Valladolid

    Valladolid

Other trials in Spain

Switzerland4 sites

  • Istituto Oncologico della Svizzera Italiana

    Bellinzona

  • Universitätsklinik für Medizinische Onkologie, Inselspital

    Bern

  • Hôpitaux universitaires de Genève (HUG)

    Geneva

  • Kantonsspital St. Gallen

    Sankt Gallen

Other trials in Switzerland

France3 sites

  • Chu Angers

    Angers

  • Centre Hospitalier d'Avignon

    Avignon

  • Centre Léon Bérard

    Lyon

Other trials in France

Italy1 site

  • AO SM Misericorida Perugia

    Perugia

Other trials in Italy

Netherlands1 site

  • Netherlands Cancer Institute (NKI)

    Amsterdam

Other trials in Netherlands

United Kingdom1 site

  • The Royal Marsden NHS Foundation Trust

    London

Other trials in United Kingdom

About this study

Official title: A Multicentre Single-arm Phase II Trial of Amivantamab, Lazertinib Plus Bevacizumab in Patients With EGFR-mutant Advanced NSCLC With Progression on Previous Third-generation EGFR-TKI

AMAZE-lung is a multicenter single-arm phase II trial. The protocol treatment consists of amivantamab, lazertinib and bevacizumab (Zirabev®), given in a three-weekly regimen. The primary objective of the trial is to assess the efficacy of amivantamab and bevacizumab added to continued treatment with the third-generation EGFR-TKI lazertinib, in patients with EGFR-mutant advanced NSCLC, who have been previously treated with a third-generation EGFR-TKI in order to provide data on treatment effect and sample size required for a future phase III trial.

In addition, the safety of the treatment combination will be evaluated.

Being tested
Amivantamab, Lazertinib, Zirabev
Keywords
EGFR-mutant advanced non-squamous NSCLC
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.

  • AmivantamabDrug

    Amivantamab is given at a fixed dose of 1750 mg (if baseline body weight is <80 kg) or 2100 mg (if baseline body weight is ≥80 kg), i.v. every 3 weeks, until disease progression, or intolerable toxicity.

  • LazertinibDrug

    Lazertinib is given at a dose of 240 mg, orally, once daily. Treatment with lazertinib continues until disease progression or intolerable toxicities.

  • ZirabevDrug

    Bevacizumab (Zirabev®) is administered at a dose of 15mg/kg, i.v. every 3 weeks, until disease progression, or intolerable toxicity.

Study groups in NCT05601973
Study groupRoleWhat they receive
Treatment ArmExperimentalAmivantamab (fixed dose of 1750 mg (or 2100 mg, i.v. every 3 weeks, until disease progression, or intolerable toxicity) PLUS Lazertinib (240 mg, orally, once daily, until disease progression or intolerable toxicities) PLUS Bevacizumab (Zirabev® is administered at a dose of 15mg/kg, i.v. every 3 weeks, until disease progression, or intolerable toxicity).
Receives: Drug: Amivantamab; Drug: Lazertinib; Drug: Zirabev

What is being measured

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

  1. Efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or lazertinib)

    The primary endpoint to assess the efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or lazertinib) is the objective response rate (ORR), investigator assessed, at 12 weeks according to RECIST v1.1. ORR is defined as the rate of patients, among all enrolled patients, that achieve a best overall response [complete response (CR) or partial response (PR)] across all post-enrolment tumour-assessment time-points.

    Measured: from date of enrolment until 12 weeks of follow-up.

Secondary outcomes (5)

  1. To evaluate secondary measures of clinical efficacy including progression-free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR).

    Secondary endpoint: Duration of response (DoR)

    Measured: from date of first documented objective response (CR or PR) to the date of first documented progression/relapse or death, assessed up to 24 months.

  2. To evaluate secondary measures of clinical efficacy including progression-free survival

    Secondary endpoint: Progression-free survival (PFS) according to RECIST v1.1

    Measured: time from enrolment date until documented progression or death or date of last tumour assessment (for patient without PFS), assessed up to 24 months

  3. To evaluate secondary measures of clinical efficacy including progression-free survival

    Secondary endpoint: Disease control rate (DCR) according to RECIST v1.1 patients, among all enrolled patients, that achieve CR or PR or disease stabilisation at 12 weeks.

    Measured: from date of enrolment until 12 weeks after enrolment.

  4. To evaluate secondary measures of clinical efficacy including progression-free survival

    Secondary endpoint: Overall survival (OS)

    Measured: from date of enrolment until death from any cause. Censoring will occur at the last follow-up date (appr. 24 months after FPI).

  5. Safety and tolerability of the treatment based on any reported adverse events (any-cause, treatment-related, AEs leading to dose interruptions, withdrawal of treatment, and death as well as severe, serious and selected adverse events) and deaths

    Secondary endpoint: Safety and tolerability (CTCAE v5.0)

    Measured: From first patient enrolled until last patient last visit (about 24 months after FPI).

Timeline

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

  1. First posted1 Nov 2022
  2. Study start27 Mar 2023
  3. Primary completion24 Aug 2024
  4. Study completion30 Sep 2026 (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
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
60 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05601973
Sponsor's protocol ID
ETOP 18-21
Other IDs
2021-002337-42
Acronym
AMAZE-lung
Status last verified
Jan 2026
First submitted
26 Oct 2022
Last updated
21 Jan 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes

Publications

  • Soo RA, Popat S, Dafni U, de Langen AJ, Nadal E, Iranzo P, Fruh M, Perol M, Metro G, Sala MA, Cucurull Salamero M, Cerciello F, Addeo A, Domine M, Oulkhouir Y, Cloarec N, Lopez Castro R, Froesch P, Roschitzki-Voser H, Ruepp B, Gasca-Ruchti A, Dellaporta T, Peters S, Stahel RA; ETOP AMAZE-lung collaborators. Combined amivantamab, lazertinib, and bevacizumab in patients with EGFR-mutant advanced non-small-cell lung cancer with acquired resistance to a third-generation EGFR tyrosine-kinase inhibitor (ETOP 18-21 AMAZE-lung): a prospective, international, multicentre, single-arm, phase 2 trial. Lancet Respir Med. 2026 Oct 5:S2213-2600(26)00203-1. doi: 10.1016/S2213-2600(26)00203-1. Online ahead of print.

    PubMed 42833236

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Amivantamab, Lazertinib and Zirabev in people with Non Small Cell Lung Cancer, run by ETOP IBCSG Partners Foundation at 18 sites in 6 countries.

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 19 inclusion and 54 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 21 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 18 sites in Spain, Switzerland, France, Italy, Netherlands and 1 more country. 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?

Efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or lazertinib) (time frame: from date of enrolment until 12 weeks of follow-up.). 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 NCT05601973, 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 21 Jan 2026.

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