AMIVANTAMAB for Non-small cell lung cancer (EGFR-mutated), advanced or metastatic

Inclusion criteria

• {"criterion_text":"- 1. Be ≥18 years of age (or the legal age of majority in the jurisdiction in which the study is taking place, whichever is greater) at the time of informed consent.\n- 2. Have histologically or cytologically confirmed, locally advanced or metastatic NSCLC that is treatment-naïve and not amenable to curative therapy including surgical resection or (chemo)radiation. Adjuvant or neoadjuvant therapy for Stage I or Stage II disease is allowed if administered more than 12 months prior to the development of locally advanced or metastatic disease.\n- 3. Have a tumor that harbors an EGFR exon 19del or exon 21 L858R substitution, as detected by an FDA-approved or other validated test in a CLIA-certified laboratory (sites in the United States) or an accredited local laboratory (sites outside of the United States) in accordance with site standard of care. (Note: A copy of the test report documenting the EGFR mutation must be included in the participant records.)\n- 4. Participants with a history of brain metastases must have had all lesions treated as clinically indicated (ie, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization, and the participant can be receiving no greater than 10 mg prednisone or equivalent daily for the treatment of intracranial disease.\n- 6. Have an ECOG performance status of 0 to 1 (Appendix 7: Eastern Cooperative Oncology Group (ECOG) Performance Scale).\n- 14. A participant must agree not to be pregnant, breastfeeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of amivantamab or lazertinib.\n- Sub-study: Participants must have new-onset or persistent (defined as non-responsive to standard of care [SoC]) Grade >=2 specific DAEIs of the scalp, face, or body, as defined by NCI CTCAE Grading v5.0 for DAEIs (excluding paronychia)"}

Exclusion criteria

• {"criterion_text":"- 1. History of uncontrolled illness, including but not limited to - Uncontrolled diabetes - Ongoing or active infection (includes infection requiring treatment with antimicrobial therapy [participants will be required to complete antibiotics 1 week prior to starting background anticancer treatment] or diagnosed or suspected viral infection. For the amivantamab SC Expansion cohort, this includes active localized serious infections. - Active bleeding diathesis - Impaired oxygenation requiring continuous oxygen supplementation - Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product, or previous significant bowel resection that would preclude adequate absorption of background anticancer treatment or doxycycline/minocycline - Psychiatric illness, social situation, or any other circumstances that would limit compliance with study requirements - Any ophthalmologic condition that is clinically unstable - Pre-existing skin condition that would prevent adequate evaluations of dermatologic toxicity, as determined by the investigator\n- 2. Medical history of ILD, including drug-induced ILD or radiation pneumonitis\n- 3. Known allergy, hypersensitivity, or intolerance to the excipients of amivantamab, lazertinib, or to tetracyclines, doxycycline, minocycline, timolol*, ruxolitinib*, zinc*, corticosteroids* or their excipients or to any component of the enhanced dermatologic management (refer to the IBs or product labels). NOTE: For the amivantamab SC Expansion cohort, participants with known allergies, hypersensitivity, intolerance to excipients or contraindications to propranolol will not be excluded from the study. However, if these participants experience scalp DAEIs during the study, propranolol should not be initiated. Participants should receive treatment with clobetasol 0.05% shampoo only. *Only applicable for participants to be included in the amivantamab SC expansion cohort\n- 4. History of clinically significant cardiovascular disease including, but not limited to, the following: - Diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of background anticancer treatment(s), or any of the following within 6 months prior to the first dose of background anticancer treatment(s): 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 catheterassociated clots, are not exclusionary. - Significant genetic predisposition to VTEs such as Factor V Leiden. - Prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines. Participants with history of VTE K1 month prior to the first dose of background anticancer treatment and on appropriate therapeutic anticoagulation may be eligible. - Prolonged QTcF interval >480 msec or 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 mmHg; diastolic blood pressure >100 mm Hg. - Congestive heart failure, defined as NYHA class III-IV or hospitalization for congestive heart failure (any NYHA class) within 6 months of treatment initiation at C1D1 (Appendix 10: New York Heart Association (NYHA) Criteria). - Pericarditis/clinically significant pericardial effusion. - Myocarditis. - Baseline LVEF below the institution’s lower limit of normal at screening, as assessed by echocardiogram or MUGA scan.\n- 6. Participant has received any prior systemic treatment at any time for locally advanced Stage III or metastatic Stage IV disease (adjuvant or neoadjuvant therapy for Stage or II disease is allowed if administered more than 12 months prior to the development of locally advanced or metastatic disease).\n- 7. Participant has an active or past medical history of leptomeningeal disease.\n- 12. Has received any prior treatment with an EGFR TKI for metastatic or unresectable disease (adjuvant treatment with osimertinib is allowed if administered more than 12 months prior to the development of locally advanced or metastatic disease and all osimertinib toxicities are resolved prior to enrollment).\n- Sub-study: Participants who have received prior treatment for epidermal growth factor receptor (EGFR)-induced DAEIs with JAK inhibitors (for Cohort A) or calcineurin inhibitors (for Cohort B)"}

Primary endpoints

• {"endpoint_text":"- Incidence of Grade ≥2 DAEIs (Appendix 17: Dermatologic Adverse Events of Interest: Preferred Terms) in the first 12 weeks after initiation of amivantamab and lazertinib treatment","definition_or_measurement_approach":"Incidence of Grade ≥2 dermatologic adverse events of interest (DAEIs) as defined in Appendix 17 (Preferred Terms); grading per NCI CTCAE v5.0; measured as occurrence (incidence) within the first 12 weeks after initiation of amivantamab and lazertinib treatment."}

Spain

Earliest CTIS Part Ii Submission Date

23-02-2024

Latest Decision Or Authorization Date

19-04-2024

Processing Time Days

56

Number Of Sites

10

Number Of Participants

6

Germany

Earliest CTIS Part Ii Submission Date

19-02-2024

Latest Decision Or Authorization Date

20-03-2024

Processing Time Days

30

Number Of Sites

8

Number Of Participants

3

France

Earliest CTIS Part Ii Submission Date

29-12-2023

Latest Decision Or Authorization Date

22-03-2024

Processing Time Days

84

Number Of Sites

3

Number Of Participants

6

Primary sponsor

Full Name

Janssen - Cilag International

Organisation Type

Pharmaceutical company

Country Of Registered Address

Belgium

Third parties

• {"country":"United States","full_name":"Eresearchtechnology Inc.","duties_or_roles":"code 7","organisation_type":"Pharmaceutical company"}
• {"country":"United Kingdom","full_name":"Mapi Research Trust","duties_or_roles":"PRO license agreement","organisation_type":"Patient organisation/association"}
• {"country":"United States","full_name":"Almac Clinical Technologies LLC","duties_or_roles":"code 3","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Iqvia Rds Inc.","duties_or_roles":"code 6","organisation_type":"Pharmaceutical company"}
• {"country":"Ireland","full_name":"Icon Clinical Research Limited","duties_or_roles":"translation services","organisation_type":"Pharmaceutical company"}
• {"country":"United States","full_name":"Ancillare LP","duties_or_roles":"Provision of cosmetic product (Lipikar moisturiser)","organisation_type":"Pharmaceutical company"}