A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer

Phase 3Active Not RecruitingNCT04487080

Janssen Research & Development, LLC1,074 enrolled

Overview

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).

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Enrollment

1,074

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

AmivantamabDRUG

Participants will receive amivantamab intravenously.

OsimertinibDRUG

Participants will receive osimertinib capsules orally.

LazertinibDRUG

Participants will receive lazertinib tablets orally.

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (267)

Outcomes

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)

PFS was defined as the time from randomization until the date of objective disease progression based on BICR using RECIST version 1.1 or death (by any cause) the absence of progression, whichever came first. Disease progression was defined using RECIST 1.1 as a 20 percent (%) increase in the sum of diameters of target measurable lesions above the smallest sum observed, with a minimum absolute increase of 5 millimeters (mL). Participants who have not progressed or have not died at the time of analysis were censored at the time of the latest date of their last evaluable RECIST version 1.1 assessment.

Time frame: From randomization to either disease progression or death whichever occurs first (up to 32.8 months)

Secondary Outcomes

Overall Survival (OS)

Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.

Time frame: Approximately 60 months (time from the date of randomization until the date of death due to any cause)

Objective Response Rate (ORR)

ORR is defined as the percentage of participants who achieve either a complete response (CR) or partial response (PR) as defined by BICR using RECIST v1.1 criteria.

Time frame: Approximately 32.8 months

Duration of Response (DOR)

DOR is defined as the time from the date of first documented response (CR or PR) until the date of documented progression or death, whichever comes first, only for participants who achieve CR or PR as determined by the investigator using RECIST v1.1 criteria.

Time frame: Approximately 32.8 months

Progression-Free Survival After First Subsequent Therapy (PFS2)

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.

Participants will receive matching placebo orally.

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 257 more locations

The PFS2 is defined as the time from randomization until the date of second objective disease progression, after initiation of subsequent anticancer therapy, based on investigator assessment (after that used for PFS) or death, whichever comes first.