ETOP 18-21 AMAZE-lung: A clinical study exploring the effect of amivantamab and lazertinib plus bevacizumab treatment, in people diagnosed with advanced non-small cell lung cancer (NSCLC) that shows a change (mutation) in the EGFR gene and has spread to other parts of the body during or after treatment with osimertinib or lazertinib.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

ETOP IBCSG Partners Foundation

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Respiratory Tract Diseases [C08]

Trial duration

11 Apr 2023 → ongoing

Decision date (initial)

2024-10-03

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Janssen Pharmaceutica NV

External identifiers

EU CT number

2024-512288-29-00

EudraCT number

2021-002337-42

ClinicalTrials.gov

NCT05601973

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

The primary objective of the trial is to assess the efficacy of amivantamab and bevacizumab added to continued treatment with a third-generation EGFR-TKI (osimertinib or 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 first.

Secondary objectives 1

1. • To evaluate secondary measures of clinical efficacy including progression-free survival (PFS), overall survival (OS), duration of response (DoR), disease control rate (DCR). • To assess the safety and tolerability of the treatment.

Conditions and MedDRA coding

Patients with EGFR-mutant (L858R or del19 only) advanced non-squamous NSCLC, who have progressed on previous treatment with a third-generation EGFR-TKI.

Study design 6 periods

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 1

1. • Histologically confirmed, non-squamous NSCLC, stage IIIB/C (not suitable for radical therapy) or stage IV according to TNM classification (8th edition). • Presence of a sensitizing EGFR mutation (only patients with exon 19 deletion and/or L858R mutation are eligible) and documented T790M status, tested on site by an accredited laboratory. • Radiologically confirmed disease progression during prior treatment with osimertinib or lazertinib. Treatment with osimertinib must have been stopped at least 8 days prior to study enrollment. • Achievement of objective clinical benefit from treatment with osimertinib or lazertinib (e.g. documented partial response (PR) or complete response (CR) or stable disease (SD) for ≥6 months under treatment with osimertinib or lazertinib). • Measurable disease as defined by RECIST v1.1. • Age ≥18 years • Eastern Cooperative Oncology Group (ECOG) performance status 0 - 2. • Life expectancy of ≥ 12 weeks • Adequate hematologic, renal and liver function. • Written patient information and informed consent.

Exclusion criteria 1

1. • 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 or hepatitis C antibody. • Patients with other clinically active infectious liver disease. • Patients who are positive for HIV. • Patients with active cardiovascular disease. • 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. • 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. • Patients with uncontrolled illness. • History of hypersensitivity to either the drug substance or any excipients in amivantamab, lazertinib and/ or bevacizumab. • Prior chemotherapy. • 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.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Objective response rate (ORR) at 12 weeks according to RECIST v1.1

Secondary endpoints 1

1. • Duration of Response (DoR) • Progression-free survival (PFS) according to RECIST v1.1 • Disease control rate (DCR) according to RECIST v1.1 • Overall survival (OS) • Safety and tolerability (CTCAE v5.0)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

ETOP IBCSG Partners Foundation

Sponsor organisation

ETOP IBCSG Partners Foundation

Address

Effingerstrasse 33

City

Bern

Postcode

3008

Country

Switzerland

Scientific contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Public contact point

Organisation

ETOP IBCSG Partners Foundation

Contact name

ETOP IBCSG Partners Regulatory Office

Third parties 3

Locations

4 EU/EEA countries · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 38 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

4 submissions — initial application plus substantial / non-substantial modifications