Amivantamab for Non-small cell lung cancer (EGFR exon 20 insertion-mutated, locally advanced or metastatic)

Inclusion criteria

• {"criterion_text":"- Participant must have histologically or cytologically confirmed, locally advanced or metastatic, nonsquamous NSCLC with documented primary EGFR Exon 20ins activating mutation (a copy of the mutation analysis must be submitted during screening) performed by a Clinical Laboratory Improvement Amendments (CLIA)-certified (US sites) or an accredited (outside of the US) local laboratory."}
• {"criterion_text":"- Participant must have measurable disease according to RECIST v1.1. If only one measurable lesion exists, it may be used for the screening biopsy (if required for submission of tumor tissue) if the baseline tumor assessment scans are performed ≥14 days after the biopsy."}
• {"criterion_text":"- Participant must have ECOG performance status 0 or 1."}
• {"criterion_text":"- Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion or platelet transfusion within 7 days prior to the date of the laboratory test. - Hemoglobin ≥10 g/dL - Absolute neutrophil count ≥1.5109/L, without use of granulocyte colonystimulating factor (G-CSF) within 10 days prior to the date of the test - Platelets ≥100109/L - ALT and aspartate aminotransferase (AST) ≤3×upper limit of normal (ULN) - Total bilirubin ≤1.5ULN (participants with Gilbert’s syndrome can enroll if conjugated bilirubin is within normal limits) - Creatinine clearance >50 mL/min as measured or calculated by Cockcroft-Gault formula"}

Exclusion criteria

• {"criterion_text":"- Participant has received any prior systemic treatment for locally advanced or metastatic disease, with the following exceptions: - Prior adjuvant or neoadjuvant platinum-based doublet chemotherapy is allowed, if completed at least 12 months prior to signing the study ICF. - Localized radiotherapy to the lung must be completed at least 6 months prior to randomization. Palliative radiation to other sites must be completed at least 7 days prior to randomization. - Prior monotherapy with an approved EGFR TKI (ie, gefitinib, erlotinib, afatinib, dacomitinib, or osimertinib) as non-standard first-line therapy for the treatment of locally advanced or metastatic disease is allowed, if: 1) treatment duration did not exceed 8 weeks; 2) lack of disease response was documented (radiographically) by an increase in tumor burden (a copy of the computerized tomography [CT] report showing increase in tumor burden from baseline should be submitted); 3) associated toxicities have resolved to baseline; and 4) the EGFR TKI was discontinued at least 2 weeks or 4 half-lives prior to randomization, whichever is longer. Prior therapy with investigational EGFR TKI agents targeting Exon 20ins mutations, including TAK788 or poziotinib, is not allowed."}
• {"criterion_text":"- Participant has evidence of synchronous NSCLC disease (as suggested by genetic characterization or radiographic appearance)."}
• {"criterion_text":"- Participant has untreated brain metastases (a participant with definitively, locally treated metastases who is clinically stable, asymptomatic, and off corticosteroid treatment for at least 2 weeks prior to randomization is eligible). If brain metastases are diagnosed on Screening imaging, the participant may be rescreened for eligibility after definitive treatment."}
• {"criterion_text":"- Participant has history of spinal cord compression that has not been treated definitively with surgery or radiation."}
• {"criterion_text":"- Participant has a medical history of ILD, including drug-induced ILD, or radiation pneumonitis."}
• {"criterion_text":"- Participant has a history of clinically significant cardiovascular disease including, but not limited to: - Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to randomization or any of the following within 6 months prior to randomization: myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary. - Prolonged corrected QT interval by Fridericia’s (QTcF) >480 msec, clinically significant cardiac arrhythmia, or electrophysiologic disease (eg, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate) - Uncontrolled (persistent) hypertension: systolic blood pressure >160 mm Hg; diastolic blood pressure >100 mm Hg - Congestive heart failure defined as New York Heart Association (NYHA) Class III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of study Day 1 (refer to Appendix 6: New York Heart Association Criteria) - Pericarditis/clinically significant pericardial effusion - Myocarditis - Baseline left ventricular ejection fraction below the lower limit of normal as assessed by screening echocardiogram (ECHO) or multigated acquisition scan."}
• {"criterion_text":"- Participant has an uncontrolled illness, including but not limited to the following: - Diabetes - Ongoing or active bacterial infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week before randomization]), symptomatic viral infection, or any other clinically significant infection - Active bleeding diathesis - Impaired oxygenation requiring supplemental oxygen - Psychiatric illness/social situation that would limit compliance with study requirements"}
• {"criterion_text":"- Participant has any condition for which, in the opinion of the investigator, participation would not be in the best interest of the participant (eg, compromise the well-being) or that could prevent, limit, or confound the protocol-specified assessments."}

Primary endpoints

• {"endpoint_text":"- Progression-Free Survival (PFS) (using RECIST v1.1 guidelines), as assessed by blinded independent central review (BICR)","definition_or_measurement_approach":"Assessment by RECIST v1.1 guidelines and adjudicated by blinded independent central review (BICR)."}

Hungary

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

02-12-2024

Processing Time Days

312

Number Of Sites

1

Number Of Participants

1

Belgium

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

28-10-2025

Processing Time Days

642

Number Of Sites

2

Number Of Participants

3

Germany

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

15-07-2025

Processing Time Days

537

Number Of Sites

1

Number Of Participants

2

Portugal

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

29-10-2025

Processing Time Days

643

Number Of Sites

2

Number Of Participants

4

France

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

28-10-2025

Processing Time Days

642

Number Of Sites

4

Number Of Participants

7

Poland

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

31-10-2025

Processing Time Days

645

Number Of Sites

3

Number Of Participants

6

Spain

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

03-11-2025

Processing Time Days

648

Number Of Sites

5

Number Of Participants

29

Italy

Earliest CTIS Part Ii Submission Date

25-01-2024

Latest Decision Or Authorization Date

17-12-2025

Processing Time Days

692

Number Of Sites

4

Number Of Participants

12

Primary sponsor

Full Name

Janssen - Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Contract research organisations

Name

Pra Health Sciences Inc.

Name

Signant Health Global LLC

Name

Bioclinica Inc.

Responsibilities

Imaging

Name

Labcorp Central Laboratory Services S.a.r.l.

Name

Covance Bioanalytical Services LLC

Third parties

• {"country":"United States","full_name":"Omnitrace Corp.","duties_or_roles":"Investigator & Patient Engagement Portfolio Team","organisation_type":"Non-Pharmaceutical company"}
• {"country":"United States","full_name":"Bioclinica Inc.","duties_or_roles":"Imaging","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"Switzerland","full_name":"Labcorp Central Laboratory Services S.a.r.l.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Covance Bioanalytical Services LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"Central ECG","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Guardant Health Inc.","duties_or_roles":"ctDNA testing","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Smithers PDS LLC","duties_or_roles":"PK/immunogenicity analysis","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Signant Health Global LLC","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Pra Health Sciences Inc.","duties_or_roles":"","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"EPL Pathology Archives LLC","duties_or_roles":"Archiving of future research sample after the study ended","organisation_type":"Laboratory/Research/Testing facility"}
• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"ePROs","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Qd Solutions Inc.","duties_or_roles":"Patient recruitment tool central printing","organisation_type":"Non-Pharmaceutical company"}