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JOURNAL ONKOLOGIE – STUDIE
AMAZE-lung

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

Rekrutierend

NCT-Nummer:
NCT05601973

Studienbeginn:
März 2023

Letztes Update:
05.04.2024

Wirkstoff:
Amivantamab, Lazertinib, Zirabev

Indikation (Clinical Trials):
Lung Neoplasms, Carcinoma, Non-Small-Cell Lung

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 2

Sponsor:
ETOP IBCSG Partners Foundation

Collaborator:
Janssen Pharmaceuticals

Studienleiter

Ross Soo, MD FRACP
Study Chair
National University Hospital, Singapore

Kontakt

Studienlocations
(3 von 21)

Alle anzeigen

Studien-Informationen

Brief 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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

1. 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.):
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.



Secondary outcome:

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

2. To evaluate secondary measures of clinical efficacy including progression-free survival (Time Frame - time from enrolment date until documented progression or death or date of last tumour assessment (for patient without PFS), assessed up to 24 months):
Secondary endpoint: Progression-free survival (PFS) according to RECIST v1.1

3. To evaluate secondary measures of clinical efficacy including progression-free survival (Time Frame - from date of enrolment until 12 weeks after enrolment.):
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.

4. To evaluate secondary measures of clinical efficacy including progression-free survival (Time Frame - from date of enrolment until death from any cause. Censoring will occur at the last follow-up date (appr. 24 months after FPI).):
Secondary endpoint: Overall survival (OS)

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 (Time Frame - From first patient enrolled until last patient last visit (about 24 months after FPI).):
Secondary endpoint: Safety and tolerability (CTCAE v5.0)

Geprüfte Regime

  • Amivantamab:
    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.
  • Lazertinib:
    Lazertinib is given at a dose of 240 mg, orally, once daily. Treatment with lazertinib continues until disease progression or intolerable toxicities.
  • Zirabev:
    Bevacizumab (Zirabev®) is administered at a dose of 15mg/kg, i.v. every 3 weeks, until disease progression, or intolerable toxicity.

Quelle: ClinicalTrials.gov


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