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

Janssen (J&J Innovative Medicine)

Status and phase: Active, not recruiting; Phase 3

Conditions: Carcinoma, Non-Small-Cell Lung

Treatments: Drug: Lazertinib; Drug: Amivantamab; Drug: Osimertinib; Drug: Placebo

Study type: Interventional

Funder types: Industry

Identifiers

NCT04487080

2020-000743-31 (EudraCT Number)

73841937NSC3003 (Other Identifier)

CR108856

Details and patient eligibility

About

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).

Full description

Worldwide, lung cancer is the most commonly diagnosed cancer. In NSCLC the most prevalent actionable driver mutations result in the activation of epidermal growth factor receptor (EGFR). Osimertinib and Lazertinib are EGFR tyrosine kinase inhibitors (TKIs). Amivantamab is a novel bispecific antibody that targets the extracellular domain of both EGFR and MET and can inhibit tumor growth driven by EGFR and mesenchymal-epithelial transition (MET) receptors. Lazertinib inhibits primary activating Exon 19dell and Exon 21 L858R substitution EGFR mutations, and the EGFR T790M+ resistance mutation. The hypothesis is that the amivantamab and lazertinib combination (Arm A) will demonstrate superior PFS compared with single-agent osimertinib (Arm B). The study consists of 3 phases: Screening Phase, Treatment Phase and Follow-up Phase. Participants will undergo response evaluation criteria in solid tumors (RECIST 1.1), pharmacokinetics, and safety evaluations (adverse events, laboratory tests, vital sign measurements, physical examinations).

Enrollment: 1,074 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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 design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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1,074 participants in 3 patient groups

Treatment Arm A (Open-label): Amivantamab and Lazertinib

Experimental group

Description:

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:

Drug: Lazertinib

Drug: Amivantamab

Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib

Active Comparator group

Description:

Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80\*3) orally once daily.

Treatment:

Drug: Placebo

Drug: Osimertinib

Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib

Experimental group

Description:

Participants will receive lazertinib 240 mg (80\*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.

Treatment:

Drug: Placebo

Drug: Lazertinib