A Phase 3, Randomized Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib Versus Lazertinib as First-Line Treatment in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer.

Official Summary

The purpose of this study is to assess the efficacy of the amivantamab and lazertinib combination, compared with osimertinib, in participants with epidermal growth factor receptor (EGFR) mutation (Exon 19 deletions \[Exon 19del\] or Exon 21 L858R substitution) positive, locally advanced or metastatic non-small cell lung cancer (NSCLC).

Eligibility Requirements

• Minimum Age: 18 Years

Study Design

• Study Type: INTERVENTIONAL
• Allocation: RANDOMIZED
• Model: PARALLEL
• Masking: TRIPLE
• Enrollment: 1,074 participants

Study Arms

• Treatment Arm A (Open-label): Amivantamab and Lazertinib (EXPERIMENTAL)
  Participants will receive amivantamab 1050 milligram (mg) intravenously (IV) for body weight less than (\<) 80 kilogram (kg) and 1400 mg for body weight greater than or equal to (\>=) 80 kg in 28-day cycles: once weekly in Cycle 1 (with a split dose on Days 1-2), and then every 2 weeks in subsequent cycles. Lazertinib will be administered 240 mg (80\*3) orally once daily.
• Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib (ACTIVE_COMPARATOR)
  Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80\*3) orally once daily.
• Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib (EXPERIMENTAL)
  Participants will receive lazertinib 240 mg (80\*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.

Interventions

• DRUG: Amivantamab — Participants will receive amivantamab intravenously.
• DRUG: Osimertinib — Participants will receive osimertinib capsules orally.
• DRUG: Lazertinib — Participants will receive lazertinib tablets orally.
• DRUG: Placebo — Participants will receive matching placebo orally.

Primary Outcomes

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) (From randomization to either disease progression or death whichever occurs first (up to 32.8 months))

Secondary Outcomes

• Overall Survival (OS) (Approximately 60 months (time from the date of randomization until the date of death due to any cause))
• Objective Response Rate (ORR) (Approximately 32.8 months)
• Duration of Response (DOR) (Approximately 32.8 months)
• Progression-Free Survival After First Subsequent Therapy (PFS2) (Approximately 60 months)
• Time to Symptomatic Progression (TTSP) (Approximately 60 months)

Eligibility Criteria

Inclusion Criteria:

* Participant must have newly diagnosed histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) that is treatment naive and not amenable to curative therapy including surgical resection or chemoradiation
* The tumor harbors exon 19 deletions (Exon 19del) or Exon 21 L858R substitution, as detected by an food and drug administration (FDA)-approved or other validated test in a clinical laboratory improvement amendments (CLIA) certified laboratory (sites in the United states \[US\]) or an accredited local laboratory (sites outside of the US) in accordance with site standard of care
* Mandatory submission of unstained tissue from tumor (in a quantity sufficient to allow for central analysis of EGFR mutation status and blood (for circulating tumor deoxyribonucleic acid \[ctDNA\], digital droplet polymerase chain reaction \[ddPCR\], and pharmacogenomic analysis)
* Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) Grade 1 or baseline level
* Participant must have at least 1 measurable lesion, according to response evaluation criteria in solid tumors (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

Exclusion Criteria:

* 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)
* Participant has an active or past medical history of leptomeningeal disease
* 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 less than or equal to (\<=) 10 milligrams per day (mg/day) prednisone or equivalent
* Participant has an active or past medical history of interstitial lung disease (ILD)/pneumonitis, including drug-induced or radiation ILD/pneumonitis
* 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
* Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study

Trial Locations

• Arizona Oncology Associates, PC - HAL, Goodyear, Arizona, United States
• Yuma Regional Medical Center, Yuma, Arizona, United States
• City of Hope Long Beach Elm, Long Beach, California, United States
• University of California Irvine, Orange, California, United States
• Rocky Mountain Cancer Centers, Lone Tree, Colorado, United States
• Cancer Specialists of North Florida, Jacksonville, Florida, United States
• University Cancer And Blood Center LLC, Athens, Georgia, United States
• East Jefferson General Hospital, Metairie, Louisiana, United States
• Maryland Oncology Hematology, PA, Columbia, Maryland, United States
• Henry Ford Hospital, Detroit, Michigan, United States
• ...and 10 more locations

Study Officials

• Janssen Research & Development, LLC Clinical Trial — STUDY_DIRECTOR
  Janssen Research & Development, LLC

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