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NCT Number: NCT04988295

A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure

The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.

Active, Not Recruiting

This study is active but is not currently recruiting participants.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 3

Primary location

CEMIC (Centro de Educación Médica e Investigaciones Clínicas), CABA, Argentina

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
  • Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
  • A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
  • Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
  • Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade <= 2 peripheral neuropathy, or Grade <= 2 hypothyroidism stable on hormone replacement)
  • A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
  • Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)

Exclusion criteria

  • Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
  • Participant with symptomatic or progressive brain metastases
  • Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
  • Participant has known small cell transformation
  • Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
  • Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines

Treatment and study plan

Lazertinib

Drug

Lazertinib will be administered orally.

Other names: JNJ-73841937, YH-25448

Amivantamab

Drug

Amivantamab will be administered as an IV infusion.

Other names: JNJ-61186372

Pemetrexed

Drug

Pemetrexed will be administered as an IV infusion.

carboplatin

Drug

Carboplatin will be administered as an IV infusion.

Primary outcomes

  1. Main Study: 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 occurred first (up to 1 year 7 months)

    PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (>=)20 percent (%) and >=5 millimeter (mm) from nadir (including baseline if it was smallest sum).

  2. Main Study + Extension Cohort: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)

    Time frame: up to 4 years 10 months

    Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.

  3. Main Study + Extension Cohort: Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review

    Time frame: Up to 4 years 10 months

Secondary outcomes

  1. Main Study+ Extension Cohort: Objective Response Rate as Assessed by Blinded Independent Central Review

    Time frame: Up to 4 years 10 months

  2. Main Study+ Extension Cohort: Overall Survival

    Time frame: Up to 4 years 10 months

  3. Main Study+ Extension Cohort: Duration of Response as Assessed by Blinded Independent Central Review

    Time frame: Up to 4 years 10 months

  4. Main Study+ Extension Cohort: Time to Subsequent Therapy

    Time frame: Up to 4 years 10 months

  5. Main Study+ Extension Cohort: Progression-free Survival (PFS) After First Subsequent Therapy (PFS2)

    Time frame: Up to 4 years 10 months

  6. Main Study+ Extension Cohort: Time to Symptomatic Progression

    Time frame: Up to 4 years 10 months

  7. Main Study+ Extension Cohort: Intracranial Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review

    Time frame: Up to 4 years 10 months

  8. Main Study: Number of Participants With Adverse Events (AEs)

    Time frame: Up to 4 years 10 months

  9. Main Study+ Extension Cohort: Number of Participants With Adverse Events (AEs) by Severity

    Time frame: Up to 4 years 10 months

  10. Main Study+ Extension Cohort: Number of Participants With Clinical Laboratory Abnormalities

    Time frame: Up to 4 years 10 months

  11. Main Study+ Extension Cohort: Serum Concentration of Amivantamab

    Time frame: Up to 4 years 10 months

  12. Main Study+ Extension Cohort: Plasma Concentration of Lazertinib

    Time frame: Up to 4 years 10 months

  13. Main Study + Extension Cohort: Number of Participants With Serum Anti-amivantamab Antibodies

    Time frame: Up to 4 years 10 months

  14. Main Study+ Extension Cohort: Change From Baseline With Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NSCLC-SAQ)

    Time frame: Up to 4 years 10 months

  15. Main Study+ Extension Cohort: Change From Baseline With European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30)

    Time frame: Up to 4 years 10 months

  16. Main Study+ Extension Cohort: Change From Baseline With Patient-Reported Outcomes Measurement Information System -Physical Function (PROMIS-PF)

    Time frame: Up to 4 years 10 months

Sponsors and collaborators

Lead sponsor

Janssen Research & Development, LLC

Industry

Registry information

Official study title

A Phase 3, Open-Label, Randomized Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With EGFR-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure

Acronym: MARIPOSA-2

Important dates

Study start
2021
Primary completion
2023
Study completion
2028
First posted
Aug 3, 2021
Registry last updated
Jul 30, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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