TriangleNCT04487080 · CITED IN SOURCE DOCUMENTS
A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
An NCI or FDA source cites this study. A citation does not establish that it applies to an individual diagnosis.
- Phase
- PHASE3
- Status at capture
- ACTIVE NOT RECRUITING
- Registry last update
- 2026-08-28
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).
Open the original ClinicalTrials.gov record → · Download preserved record
What did the study report?
Outcomes, safety and baseline populations are separate source sections. Quality-of-life measures appear under their original outcome titles.
Participant flow
Baseline characteristics
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
Overall Survival (OS)
Objective Response Rate (ORR)
Duration of Response (DOR)
Progression-Free Survival After First Subsequent Therapy (PFS2)
Time to Symptomatic Progression (TTSP)
Intracranial PFS
Incidence and Severity of Adverse Events (AEs)
Number of Participants With Clinical Laboratory Abnormalities
Number of Participants With Vital Signs Abnormalities
Number of Participants With Physical Examination Abnormalities
Serum Concentration of Amivantamab
Plasma Concentration of Lazertinib
Number of Participants With Anti-Amivantamab Antibodies
Change From Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ)
Change From Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)
Adverse events
Limitations, agreements, and source contact
Who could take part
- 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
- healthy Volunteers
- false
- minimum Age
- 18 Years
- sex
- ALL
- std Ages
- ADULT
- OLDER_ADULT
Treatment arms and interventions
- arm Groups
- 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.
- intervention Names
- Drug: Amivantamab
- Drug: Lazertinib
- label
- Treatment Arm A (Open-label): Amivantamab and Lazertinib
- type
- EXPERIMENTAL
- description
- Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80\*3) orally once daily.
- intervention Names
- Drug: Osimertinib
- Drug: Placebo
- label
- Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib
- type
- ACTIVE_COMPARATOR
- description
- Participants will receive lazertinib 240 mg (80\*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.
- intervention Names
- Drug: Lazertinib
- Drug: Placebo
- label
- Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib
- type
- EXPERIMENTAL
- interventions
- arm Group Labels
- Treatment Arm A (Open-label): Amivantamab and Lazertinib
- description
- Participants will receive amivantamab intravenously.
- name
- Amivantamab
- other Names
- JNJ-61186372
- type
- DRUG
- arm Group Labels
- Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib
- description
- Participants will receive osimertinib capsules orally.
- name
- Osimertinib
- type
- DRUG
- arm Group Labels
- Treatment Arm A (Open-label): Amivantamab and Lazertinib
- Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib
- description
- Participants will receive lazertinib tablets orally.
- name
- Lazertinib
- other Names
- JNJ-73841937 and YH-25448
- type
- DRUG
- arm Group Labels
- Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib
- Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib
- description
- Participants will receive matching placebo orally.
- name
- Placebo
- type
- DRUG
Study design
- allocation
- RANDOMIZED
- intervention Model
- PARALLEL
- masking Info
- masking
- TRIPLE
- masking Description
- Only Arm B and C will be masked to all (Double-blind).
- who Masked
- PARTICIPANT
- INVESTIGATOR
- OUTCOMES_ASSESSOR
- primary Purpose
- TREATMENT
Enrollment
- count
- 1074
- type
- ACTUAL
Registered outcome plans (not posted results)
- primary Outcomes
- description
- 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.
- measure
- Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR)
- time Frame
- From randomization to either disease progression or death whichever occurs first (up to 32.8 months)
- secondary Outcomes
- description
- Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.
- measure
- Overall Survival (OS)
- time Frame
- Approximately 60 months (time from the date of randomization until the date of death due to any cause)
- description
- 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.
- measure
- Objective Response Rate (ORR)
- time Frame
- Approximately 32.8 months
- description
- 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.
- measure
- Duration of Response (DOR)
- time Frame
- Approximately 32.8 months
- description
- 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.
- measure
- Progression-Free Survival After First Subsequent Therapy (PFS2)
- time Frame
- Approximately 60 months
- description
- TTSP is defined as the time from randomization to documentation in the electronic case report form (eCRF) of any of the following (whichever occurs earlier): onset of new symptoms or symptom worsening that is considered by the investigator to be related to lung cancer and requires either a change in anticancer treatment and/or clinical intervention to manage symptoms.
- measure
- Time to Symptomatic Progression (TTSP)
- time Frame
- Approximately 60 months
- description
- Intracranial PFS is defined as the time from randomization until the date of objective intracranial disease progression or death, whichever comes first, based on BICR using RECIST v1.1.
- measure
- Intracranial PFS
- time Frame
- Approximately 60 months
- description
- Incidence and severity of treatment emergent adverse events (TEAEs) will be reported. Any adverse event occurring at or after the initial administration of study treatment through the day of last dose plus 30 days, or until the start of subsequent anticancer therapy (if earlier), is considered to be treatment emergent.
- measure
- Incidence and Severity of Adverse Events (AEs)
- time Frame
- Approximately 60 months
- description
- Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.
- measure
- Number of Participants With Clinical Laboratory Abnormalities
- time Frame
- Approximately 60 months
- description
- Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported.
- measure
- Number of Participants With Vital Signs Abnormalities
- time Frame
- Approximately 60 months
- description
- Number of participants with physical examination abnormalities will be reported.
- measure
- Number of Participants With Physical Examination Abnormalities
- time Frame
- Approximately 60 months
- description
- Serum samples will be analyzed to determine concentrations of Amivantamab.
- measure
- Serum Concentration of Amivantamab
- time Frame
- Approximately 60 months
- description
- Plasma samples will be analyzed to determine concentrations of Lazertinib.
- measure
- Plasma Concentration of Lazertinib
- time Frame
- Approximately 60 months
Full study description
- brief 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).
Source references
- references
- citation
- Yang JC, Lu S, Hayashi H, Felip E, Spira AI, Girard N, Kim YJ, Lee SH, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Mourao Dias J, Besse B, Passaro A, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Yoshioka H, Thomas M, Nguyen D, Ou SI, Mukhedkar S, Prabhash K, D'Arcangelo M, Alatorre-Alexander J, Vazquez Limon JC, Alves S, Stroyakovskiy D, Peregudova M, Sendur MAN, Yazici O, Califano R, Gutierrez Calderon V, de Marinis F, Kim SW, Gadgeel SM, Owen S, Xie J, Sun T, Mehta J, Venkatasubramanian R, Ennis M, Fennema E, Daksh M, Roshak A, Man J, Knoblauch RE, Bauml JM, Baig M, Shah S, Sethi S, Cho BC; MARIPOSA Investigators. Overall Survival with Amivantamab-Lazertinib in EGFR-Mutated Advanced NSCLC. N Engl J Med. 2025 Oct 30;393(17):1681-1693. doi: 10.1056/NEJMoa2503001. Epub 2025 Sep 7.
- pmid
- 40923797
- type
- DERIVED
- citation
- Lee SH, Lu S, Hayashi H, Felip E, Spira AI, Girard N, Kim YJ, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Dias JM, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Chih-Hsin Yang J, Besse B, Thomas M, Shah S, Baig M, Curtin JC, Zhang J, Xie J, Sun T, Sethi S, Wang M, Fennema E, Daksh M, Ennis M, Bauml JM, Cho BC. Lazertinib Versus Osimertinib in Previously Untreated EGFR-Mutant Advanced NSCLC: A Randomized, Double-Blind, Exploratory Analysis From MARIPOSA. J Thorac Oncol. 2025 Nov;20(11):1655-1668. doi: 10.1016/j.jtho.2025.06.030. Epub 2025 Jul 3.
- pmid
- 40617394
- type
- DERIVED
- citation
- Cho BC, Lu S, Felip E, Spira AI, Girard N, Lee JS, Lee SH, Ostapenko Y, Danchaivijitr P, Liu B, Alip A, Korbenfeld E, Mourao Dias J, Besse B, Lee KH, Xiong H, How SH, Cheng Y, Chang GC, Yoshioka H, Yang JC, Thomas M, Nguyen D, Ou SI, Mukhedkar S, Prabhash K, D'Arcangelo M, Alatorre-Alexander J, Vazquez Limon JC, Alves S, Stroyakovskiy D, Peregudova M, Sendur MAN, Yazici O, Califano R, Gutierrez Calderon V, de Marinis F, Passaro A, Kim SW, Gadgeel SM, Xie J, Sun T, Martinez M, Ennis M, Fennema E, Daksh M, Millington D, Leconte I, Iwasawa R, Lorenzini P, Baig M, Shah S, Bauml JM, Shreeve SM, Sethi S, Knoblauch RE, Hayashi H; MARIPOSA Investigators. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024 Oct 24;391(16):1486-1498. doi: 10.1056/NEJMoa2403614. Epub 2024 Jun 26.
- pmid
- 38924756
- type
- DERIVED
- citation
- Cho BC, Felip E, Hayashi H, Thomas M, Lu S, Besse B, Sun T, Martinez M, Sethi SN, Shreeve SM, Spira AI. MARIPOSA: phase 3 study of first-line amivantamab + lazertinib versus osimertinib in EGFR-mutant non-small-cell lung cancer. Future Oncol. 2022 Feb;18(6):639-647. doi: 10.2217/fon-2021-0923. Epub 2021 Dec 16.
- pmid
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- type
- DERIVED
Source notices and limitations
Discovery and provenance
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- avenous Amivantamab in Combination with Lazertinib MARIPOSA The efficacy of intravenous amivantamab, in combination with lazertinib, was evaluated in MARIPOSA (NCT04487080), a randomized, active-controlled, multicenter trial. Eligible patients were required to have untreated locally advanced or metastatic NSCLC with either exon 1
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- C with Exon 19 deletion or Exon 21 L858R Substitution Mutation - MARIPOSA The efficacy of RYBREVANT, in combination with lazertinib, was evaluated in MARIPOSA [NCT04487080], a randomized, active-controlled, multicenter trial. Eligible patients were required to have untreated locally advanced or metastatic NSCLC with either exon 1
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- 14 CLINICAL STUDIES The efficacy of LAZCLUZE, in combination with amivantamab, was evaluated in MARIPOSA [NCT04487080], a randomized, active-controlled, multicenter trial. Eligible patients were required to have untreated locally advanced or metastatic NSCLC with either exon 1
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- >Evidence (amivantamab plus lazertinib):</p> <div class="pdq-content-list"><ol id="_486257"><li> The international phase III <a href="/clinicaltrials/NCT04487080">MARIPOSA</a> trial (NCT04487080) included 1,074 patients with untreated advanced or metastatic NSCLC and <em class="gene-name">EGFR</em> variants (<em class=
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- inib):</p> <div class="pdq-content-list"><ol id="_486257"><li> The international phase III <a href="/clinicaltrials/NCT04487080">MARIPOSA</a> trial (NCT04487080) included 1,074 patients with untreated advanced or metastatic NSCLC and <em class="gene-name">EGFR</em> variants (<em class="gene-name">EGFR</em> exon 19 dele
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Preserved source evidence · Not medical advice