EGFR-mutated locally advanced or metastatic Non Small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10061873 Term: Non-small cell lung cancer System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Janssen-Cilag International N.V.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant must be =18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place). 2. Participant must have histologically or cytologically confirmed, locally advanced or metastatic NSCLC not amenable to curative therapy. 3. Participant must have a tumor that was previously determined to have 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 US) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care. The biopsy must have been obtained at or after the diagnosis of advanced disease. 4. Unstained tumor tissue (in a quantity sufficient to allow for central analysis of EGFR mutation status) and blood (for ctDNA, digital droplet polymerase chain reaction [ddPCR], and pharmacogenomic analysis), both collected at or after the diagnosis of locally advanced or metastatic NSCLC 5. Any toxicities from prior anticancer therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline level. 6. Participant must have at least 1 measurable lesion, according to RECIST v1.1 that has not been previously irradiated. Measurable lesions should not have been biopsied during screening, but if only 1 non-irradiated measurable lesion exists, it may undergo a diagnostic biopsy and be acceptable as a target lesion, provided the baseline tumor assessment scans are performed at least 14 days after the biopsy. 7. Participant must have adequate organ and bone marrow function as follows, without history of red blood cell transfusion, platelet transfusion, or granulocyte colony stimulating factor (G-CSF) within 7 days prior to the date of the test. 8. Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1 9. Participant must sign an ICF (or their legally acceptable representative must sign) indicating that he or she understands the purpose of, and procedures required for, the study and is willing to participate in the study. 10. A woman of childbearing potential must have a negative serum or urine pregnancy test at screening and within 72 hours of the first dose of study treatment. 11. A woman must be either of the following: a. Not of childbearing potential b. Of childbearing potential and • practicing true abstinence during the entire period of the study, including up to 6 months after the last dose of study treatment is given; • have a sole partner who is vasectomized; • or practicing 2 highly effective methods of contraception, including 1 user independent method and a second method. Participant must agree to continue contraception throughout the study and through 6 months after the last dose of study treatment. • Note: If the childbearing potential changes after start of the study (eg, woman who is not heterosexually active becomes active, premenarchal woman experiences menarche) the woman must begin 2 highly effective methods of birth control, as described above 12. A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted reproduction during the study and for 6 months after receiving the last dose of study treatment. 13. A man must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 6 months after receiving the last dose of study treatment. A man who is sexually active with a woman of childbearing potential must agree to use
Exclusion criteria
Exclusion criteria: 1. Participant has received any prior systemic treatment for locally advanced or metastatic disease (adjuvant or neoadjuvant therapy is allowed, if administered more than 12 months prior to the development of locally advanced or metastatic disease). 2. Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening 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 randomization. 3. Participant has an active or past medical history of leptomeningeal disease. 4. Participant has spinal cord compression that has not been definitively treated with surgery or radiation or requires steroid treatment within 2 weeks prior to randomization. 5. Participant has uncontrolled tumor-related pain. 6. Participant has an active or past medical history of ILD/pneumonitis, including drug-induced or radiation ILD/pneumonitis. 7. Participant has an uncontrolled illness 8. Participant has an active malignancy other than the disease being treated under study 9. Participant has active cardiovascular disease 10. Participant has known allergy, hypersensitivity, or intolerance to the excipients used in formulation of amivantamab, lazertinib, or osimertinib, or any contraindication to the use of osimertinib. 11. Participant is currently receiving medications or herbal supplements known to be potent CYP3A4/5 inhibitors or inducers and is unable to stop use for an appropriate washout period prior to randomization. 12. Participant has received any prior treatment with an EGFR TKI. 13. Participant has received an investigational medication within 12 months before randomization or is currently enrolled in an investigational study. 14. Participant is pregnant, breast-feeding, or planning to become pregnant while enrolled in this study or within 6 months after the last dose of study treatment. 15. Participant plans to father a child while enrolled in this study or within 6 months after the last dose of study treatment. 16. 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 17. Participant has at Screening: • Positive hepatitis B (hepatitis B virus [HBV]) surface antigen (HBsAg) • Positive hepatitis C (hepatitis C virus [HCV]) antibody (anti-HCV) • Other clinically active infectious liver disease 18. Participant is positive for human immunodeficiency virus (HIV) 19. Participant had major surgery (eg, requiring general anesthesia), excluding placement of vascular access or tumor biopsy, or had significant traumatic injury within 4 weeks before signing the ICF, or will not have fully recovered from surgery, or has surgery planned during the time the participant is expected to participate in the study. Note: Participants with planned surgical procedures to be conducted under local anesthesia may participate. Full details of exclusion criteria can be found in section 5.2 of the study protocol.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with EGFR mutation (Exon 19del or Exon 21 L858R substitution) positive, locally advanced or metastatic NSCLC;Secondary Objective: The secondary objectives are to assess: 1. The clinical benefit achieved using the amivantamab and lazertinib combination compared with osimertinib in participants with EGFR mutation positive, locally advanced or metastatic NSCLC 2. The safety and tolerability of the amivantamab and lazertinib combination compared with osimertinib 3. The pharmacokinetics or immunogenicity for amivantamab and pharmacokinetics for lazertinib and assess their relationship to selected endpoints 4.The health-related quality of life and disease related symptoms in participants treated with the amivantamab and lazertinib combination compared with osimertinib 5. The efficacy of the amivantamab and lazertinib combination, compared with lazertinib monotherapy, in participants with EGFR mutation positive, locally advanced or metastatic NSCLC;Primary end point(s): Progression-free survival (PFS) according to RECIST v1.1 by blinded independent central review;Timepoint(s) of evaluation of this end point: A futility analysis based on PFS will be conducted when approximately 150 PFS events have occurred overall (all treatment arms combined). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Arm A vs Arm B: 1. Overall survival 2. Objective response rate 3. Duration of response 4. PFS after first subsequent therapy (Arm A vs Arm B) 5. Time to symptomatic progression 6. Intracranial PFS 7. Incidence of severity of adverse events and clinical laboratory abnormalities, assessment of vital signs, and physical examination abnormalities 8. Serum amivantamab and lazertinib concentrations, and anti-amivantamab antibodies 9. NSCLC-SAQ 10. EORTC-QLQ-C30 Arm A vs Arm C: 11. PFS 12. Overall survival ;Timepoint(s) of evaluation of this end point: From randomization until the date of objective disease progression or death,whichever comes first | — |
Countries
Australia, Belarus, Belgium, Brazil, Canada, China, France, Germany, Hong Kong, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Philippines, Poland, Portugal, Russian Federation, Singapore, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Registry Group
Janssen-Cilag International N.V.
Outcome results
None listed