Trial Title:
Amivantamab, Lazertinib and Bevacizumab in Patients With EGFR-mutant Advanced Non-small Cell Lung Cancer With Progression on Previous Third-generation EGFR-TKI
NCT ID:
NCT05601973
Condition:
Non Small Cell Lung Cancer
Conditions: Official terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Amivantamab-vmjw
Lazertinib
Conditions: Keywords:
EGFR-mutant advanced non-squamous NSCLC
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Amivantamab
Description:
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.
Arm group label:
Treatment Arm
Intervention type:
Drug
Intervention name:
Lazertinib
Description:
Lazertinib is given at a dose of 240 mg, orally, once daily. Treatment with lazertinib
continues until disease progression or intolerable toxicities.
Arm group label:
Treatment Arm
Intervention type:
Drug
Intervention name:
Zirabev
Description:
Bevacizumab (Zirabev®) is administered at a dose of 15mg/kg, i.v. every 3 weeks, until
disease progression, or intolerable toxicity.
Arm group label:
Treatment Arm
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 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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. Histologically confirmed non-squamous NSCLC, stage IIIB/C (not amenable to radical
therapy) or stage IV according to 8th TNM classification.
2. 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.
3. Radiologically confirmed disease progression on previous treatment with osimertinib
or lazertinib.Treatment with osimertinib must have been stopped at least 8 days
before enrolment.
4. 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).
5. Measurable disease as defined according to RECIST v1.1.
6. Age ≥18 years.
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-2.
8. Life expectancy ≥12 weeks.
9. Adequate haematological function:
- Haemoglobin ≥100 g/L,
- Absolute neutrophil count (ANC) ≥1.5× 109/L,
- Platelet count ≥75× 109/L.
10. Adequate renal function:
- Serum creatinine <1.5× ULN and calculated (Cockcroft-Gault formula) or measured
creatinine clearance >45 mL/min.
11. 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.
12. 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.
13. Written IC for trial participation must be signed and dated by the patient and the
investigator prior to any trial-related intervention.
Exclusion Criteria:
1. Patients with known small cell lung carcinoma (SCLC) transformation.
2. 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.
3. Patients with an active or past medical history of leptomeningeal disease.
4. 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.
5. Patients with unresolved adverse events (other than alopecia) from prior anticancer
therapy that have not resolved to grade ≤1 or baseline.
6. Patients with positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg)
test.
7. Patients with positive hepatitis C antibody (anti-HCV) test.
8. Patients with other clinically active infectious liver disease.
9. 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).
10. 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.
11. Patients with interstitial lung disease (ILD), including drug-induced ILD or
radiation pneumonitis.
12. Patients with a history of haemoptysis (≥2.5 mL of bright red blood per episode)
within 1 month prior to enrolment.
13. Patients with evidence of bleeding diathesis or coagulopathy (in the absence of
therapeutic anticoagulation).
14. Patients with current or recent (within 10 days before enrolment) use of aspirin
(>325 mg/day) or treatment with dipyridamole, ticlopidine, clopidogrel, and
clostazol.
15. 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.
16. Patients with serious, non-healing wound, active ulcer, or untreated bone fracture.
17. Patients who had a core biopsy or other minor surgical procedure, excluding
placement of a vascular access device, within 7 days prior to enrolment.
18. Patients who had major surgery or significant traumatic injury within 28 days prior
to enrolment.
19. Patients who had placement of a vascular access device within 2 days prior to prior
to enrolment.
20. Patients with a history of abdominal or tracheoesophageal fistula or
gastrointestinal perforation within 6 months prior to enrolment.
21. Patients with clinical signs of gastrointestinal obstruction or requirement for
routine parenteral hydration, parenteral nutrition, or tube feeding.
22. Patients with evidence of abdominal free air not explained by paracentesis or recent
surgical procedure.
23. Patients with concurrent or prior malignancy other than the disease under study.
Some exceptions require consultation with the ETOP IBCSG Partners
24. 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.
25. History of hypersensitivity to either the drug substance or any excipients in
amivantamab, lazertinib and/ or bevacizumab.
26. Prior chemotherapy for NSCLC.
27. Prior treatment with bevacizumab or another anti-angiogenic inhibitor.
28. Prior treatment with a MET/EGFR-targeting antibody.
29. 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.
30. Women who are pregnant or in the period of lactation.
31. 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.
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Locations:
Facility:
Name:
Chu Angers
Address:
City:
Angers
Country:
France
Status:
Recruiting
Contact:
Last name:
Youssef Oulkhouir, MD
Email:
Youssef.Oulkhouir@chu-angers.fr
Facility:
Name:
Centre Hospitalier d'Avignon
Address:
City:
Avignon
Country:
France
Status:
Recruiting
Contact:
Last name:
Nicolas Cloarec, MD
Email:
cloarec.nicolas@ch-avignon.fr
Facility:
Name:
Centre Léon Bérard
Address:
City:
Lyon
Country:
France
Status:
Recruiting
Contact:
Last name:
Maurice Perol, MD
Email:
maurice.perol@lyon.unicancer.fr
Facility:
Name:
SS Antonio e Biagio e Cesare Arrigo Hospital
Address:
City:
Alessandria
Country:
Italy
Status:
Withdrawn
Facility:
Name:
AO SM Misericorida Perugia
Address:
City:
Perugia
Country:
Italy
Status:
Recruiting
Contact:
Last name:
Giulio Metro, MD
Email:
giulio.metro@ospedale.perugia.it
Facility:
Name:
Netherlands Cancer Institute (NKI)
Address:
City:
Amsterdam
Country:
Netherlands
Status:
Recruiting
Contact:
Last name:
Joop de Langen, MD
Email:
j.d.langen@nki.nl
Facility:
Name:
Hospital Universitario de A Coruña
Address:
City:
A Coruña
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Joaquín Mosquera Martínez, MD
Email:
joaquin.mosquera.martinez@sergas.es
Facility:
Name:
Hospital Universitario Alicante Dr Balmis ISABIAL
Address:
City:
Alicante
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Bartomeu Massuti, MD
Email:
bmassutis@seom.org
Facility:
Name:
ICO Badalona
Address:
City:
Badalona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Marc Cucurull Salamero, MD
Email:
mcucurull@iconcologia.net
Facility:
Name:
Vall d´Hebron University Hospital VHIO
Address:
City:
Barcelona
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Patricia Iranzo, MD
Email:
piranzo@vhio.net
Facility:
Name:
Hospital Universitario Basurto
Address:
City:
Bilbao
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Mª Angeles Sala, MD
Email:
marian.salagonzalez@osakidetza.eus
Facility:
Name:
Catalan Institute of Oncology
Address:
City:
L'Hospitalet De Llobregat
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Ernest Nadal, MD
Email:
esnadal@iconcologia.net
Facility:
Name:
Hospital Universitario Fundación Jiménez Díaz
Address:
City:
Madrid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Manuel DÓMINE, MD
Email:
manueldomine@gmail.com
Facility:
Name:
Hospital clínico universitario de Valladolid
Address:
City:
Valladolid
Country:
Spain
Status:
Recruiting
Contact:
Last name:
Rafael López Castro, MD
Email:
rafalopezcastro@yahoo.es
Facility:
Name:
Istituto Oncologico della Svizzera Italiana
Address:
City:
Bellinzona
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Patrizia Frösch, MD
Email:
patrizia.froesch@eoc.ch
Facility:
Name:
Universitätsklinik für Medizinische Onkologie, Inselspital
Address:
City:
Bern
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Ferdinando MD Cerciello, MD
Email:
ferdinando.cerciello@insel.ch
Facility:
Name:
HFR Fribourg
Address:
City:
Fribourg
Country:
Switzerland
Status:
Withdrawn
Facility:
Name:
Hôpitaux universitaires de Genève (HUG)
Address:
City:
Genève
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Alfredo Addeo, MD
Email:
alfredo.addeo@hcuge.ch
Facility:
Name:
Kantonsspital St. Gallen
Address:
City:
Saint Gallen
Country:
Switzerland
Status:
Recruiting
Contact:
Last name:
Martin Früh, MD
Email:
martin.frueh@kssg.ch
Facility:
Name:
The Royal Marsden NHS Foundation Trust
Address:
City:
London
Country:
United Kingdom
Status:
Recruiting
Contact:
Last name:
Sanjay Popat, MD
Email:
sanjay.popat@rmh.nhs.uk
Start date:
March 27, 2023
Completion date:
September 30, 2026
Lead sponsor:
Agency:
ETOP IBCSG Partners Foundation
Agency class:
Other
Collaborator:
Agency:
Janssen Pharmaceuticals
Agency class:
Industry
Source:
ETOP IBCSG Partners Foundation
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05601973
