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

NCT05601973 | Active Not Recruiting Phase 2 DMC

• 2 other identifiers: ETOP 18-212021-002337-42
• Study Type: interventional
• Target: 60
• Locations: 6 countries
• Sites: 18

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.

Conditions

Non Small Cell Lung Cancer

Keywords

EGFR-mutant advanced non-squamous NSCLC

Outcome Measures

Primary Outcomes (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.

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

Secondary Outcomes (5)

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

  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.

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

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

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

  from date of enrolment until 12 weeks after enrolment.

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

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

• 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

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

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Amivantamab (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).

Drug: Amivantamab; Drug: Lazertinib; Drug: Zirabev

Interventions

Lazertinib DRUG

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

Treatment Arm

Zirabev DRUG

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

Treatment Arm

Amivantamab DRUG

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.

Treatment Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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:

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• ETOP IBCSG Partners Foundation: lead
• Janssen Pharmaceuticals: collaborator

Study Sites (18)

Chu Angers

Angers, France

Location

Centre Hospitalier d'Avignon

Avignon, France

Location

Centre Léon Bérard

Lyon, France

Location

AO SM Misericorida Perugia

Perugia, Italy

Location

Netherlands Cancer Institute (NKI)

Amsterdam, Netherlands

Location

Hospital Universitario de A Coruña

A Coruña, Spain

Location

Hospital Universitario Alicante Dr Balmis ISABIAL

Alicante, Spain

Location

ICO Badalona

Badalona, Spain

Location

Vall d´Hebron University Hospital VHIO

Barcelona, Spain

Location

Hospital Universitario Basurto

Bilbao, Spain

Location

Catalan Institute of Oncology

L'Hospitalet de Llobregat, Spain

Location

Hospital Universitario Fundación Jiménez Díaz

Madrid, Spain

Location

Hospital clínico universitario de Valladolid

Valladolid, Spain

Location

Istituto Oncologico della Svizzera Italiana

Bellinzona, Switzerland

Location

Universitätsklinik für Medizinische Onkologie, Inselspital

Bern, Switzerland

Location

Hôpitaux universitaires de Genève (HUG)

Geneva, Switzerland

Location

Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

The Royal Marsden NHS Foundation Trust

London, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

amivantamab; lazertinib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Ross Soo, MD FRACP

  National University Hospital, Singapore

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 26, 2022
• First Posted: November 1, 2022
• Study Start: March 27, 2023
• Primary Completion: August 24, 2024
• Study Completion (Estimated): September 30, 2026
• Last Updated: January 21, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP

Locations

ES (8); GB (1); FR (3); IT (1); CH (4); NL (1)