EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer harboring EGFR Exon 19del or L858R mutations
Conditions
Interventions
• Arm A: participants will be assigned to open label treatment with the
combination of amivantamab (1050 mg for body weight =80 kg by intravenous [IV] infusion, once weekly for the first 4 weeks
and
Sponsors
Janssen-Cilag
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1. Participant must be >=18 years of age 2. Criterion modified per Amendment 1 2.1 Participant must have newly diagnosed, histologically or cytologically confirmed, locally advanced or metastatic NSCLC that is treatment naïve and not amenable to curative therapy including surgical resection or chemoradiation. 3. Criterion modified per Amendment 1. 3.1 The tumor (meeting criteria described in Inclusion Criterion no. 2) harbors 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. (Note: A copy of the test report documenting the EGFR mutation must be included in the participant records and must lso be submitted to the sponsor.) 4. Criterion modified per Amendment 1. 4.1 Mandatory submission of unstained tissue from tumor meeting criteria described in Inclusion Criterion no. 2 (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). See Section 8.7. 5. Any toxicities from prior anticancer therapy must have resolved to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or baseline level. 6. at least 1 measurable lesion, according to RECIST v1.1 that has not been previously irradiated. Full details of inclusion criteria can be found in section 5.1 of the study protocol.
Exclusion criteria
Exclusion criteria: 1. Criterion modified per Amendment 2. 1.1 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 I or II disease is allowed, if administered more than 12 months prior to the development of locally advanced or metastatic disease). 2. Criterion modified per Amendment 1. 2.1 Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. 3. Participant has an active or past medical history of leptomeningeal disease. 4. Criterion modified per Amendment 1. 4.1 Participant with untreated spinal cord compression. A participant that has been definitively treated with surgery or radiation and has a stable neurological status for at least 2 weeks prior to randomization is eligible provided they are off corticosteroid treatment or receiving low-dose corticosteroid treatment
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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 Endpoint • PFS (using RECIST v1.1 guidelines), as assessed by blinded independent central review | — |
Secondary
| Measure | Time frame |
|---|---|
| a) To further assess the clinical benefit achieved using the amivantamab and lazertinib combination compared with osimertinib in participants with EGFR mutation positive, locally advanced or metastatic NSCLC endpoints • Overall survival • Objective response rate • Duration of response • PFS after first subsequent therapy (PFS2) • Time to symptomatic progression • Intracranial PFS b)To evaluate the safety and tolerability of the amivantamab and lazertinib combination compared with osimertinib endpoint • Incidence and severity of adverse events and laboratory abnormalities | — |
Countries
Netherlands
Outcome results
None listed