Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04487080
Recruitment Status : Recruiting
First Posted : July 27, 2020
Last Update Posted : October 19, 2020
Sponsor:
Information provided by (Responsible Party):
Janssen Research & Development, LLC

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).

Condition or disease Intervention/treatment Phase
Carcinoma, Non-Small-Cell Lung Drug: Amivantamab Drug: Osimertinib Drug: Lazertinib Drug: Placebo Phase 3

Detailed 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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 1000 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Masking Description: Only Arm B and C will be masked to all (Double-blind).
Primary Purpose: Treatment
Official Title: 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.
Actual Study Start Date : September 30, 2020
Estimated Primary Completion Date : April 30, 2024
Estimated Study Completion Date : November 20, 2025

Resource links provided by the National Library of Medicine

Drug Information available for: Osimertinib

Arm Intervention/treatment
Experimental: Treatment Arm A (Open-label): Amivantamab and Lazertinib
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.
Drug: Amivantamab
Participants will receive amivantamab intravenously.
Other Name: JNJ-61186372

Drug: Lazertinib
Participants will receive lazertinib tablets orally.
Other Name: JNJ-73841937 and YH-25448

Active Comparator: Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib
Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80*3) orally once daily.
Drug: Osimertinib
Participants will receive osimertinib capsules orally.

Drug: Placebo
Participants will receive matching placebo orally.

Experimental: Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib
Participants will receive lazertinib 240 mg (80*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.
Drug: Lazertinib
Participants will receive lazertinib tablets orally.
Other Name: JNJ-73841937 and YH-25448

Drug: Placebo
Participants will receive matching placebo orally.




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) According to RECIST v1.1 by Blinded Independent Central Review (BICR) [ Time Frame: Up to approximately 42 months ]
    PFS is defined as the time from randomization until the date of objective disease progression or death, whichever occured first, based on BICR using response evaluation criteria in solid tumors (RECIST) v1.1.


Secondary Outcome Measures :
  1. Overall Survival (OS) [ Time Frame: Up to approximately 60 months (time from the date of randomization until the date of death due to any cause) ]
    Overall Survival is defined as the time from the date of randomization to the date of participant's death due to any cause.

  2. Objective Response Rate (ORR) [ Time Frame: Up to approximately 42 months ]
    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.

  3. Duration of Response (DOR) [ Time Frame: Up to approximately 42 months ]
    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.

  4. Progression-Free Survival After First Subsequent Therapy (PFS2) [ Time Frame: Up to approximately 42 months ]
    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.

  5. Time to Symptomatic Progression (TTSP) [ Time Frame: Up to approximately 42 months ]
    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.

  6. Intracranial PFS [ Time Frame: Up to approximately 42 months ]
    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.

  7. Incidence and Severity of Adverse Events (AEs) [ Time Frame: Up to approximately 60 months ]
    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.

  8. Number of Participants with Clinical Laboratory Abnormalities [ Time Frame: Up to approximately 60 months ]
    Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.

  9. Number of Participants with Vital Signs Abnormalities [ Time Frame: Up to approximately 60 months ]
    Number of participants with vital signs abnormalities (temperature, heart rate, respiratory rate, oxygen saturation, blood pressure) will be reported.

  10. Number of Participants with Physical Examination Abnormalities [ Time Frame: Up to approximately 60 months ]
    Number of participants with physical examination abnormalities will be reported.

  11. Serum Concentration of Amivantamab [ Time Frame: Up to approximately 42 months ]
    Serum samples will be analyzed to determine concentrations of amivantamab.

  12. Plasma Concentration of Lazertinib [ Time Frame: Up to approximately 42 months ]
    Plasma samples will be analyzed to determine concentrations of lazertinib.

  13. Number of Participants with Anti-Amivantamab Antibodies [ Time Frame: Up to approximately 42 months ]
    Number of participants with antibodies to amivantamab will be reported.

  14. Change from Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ) [ Time Frame: Baseline Up to approximately 42 months ]
    The NSCLC-SAQ contains 7 items that assess cough, pain, dyspnea, fatigue, and poor appetite over a 7-day recall period. Each multi-item scale and individual item will be summarized using count and percent by visit.

  15. Change from Baseline in European Organization of Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC-QLQ-C30) [ Time Frame: Baseline Up to approximately 42 months ]
    EORTC-QLQ-C30 is a core 30-item questionnaire for evaluating the health-related quality of life (HRQoL) of participants participating in cancer clinical studies.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Participant must have histologically or cytologically confirmed, locally advanced or metastatic non-small cell lung cancer (NSCLC) not amenable to curative therapy
  • Participant must have a tumor that was previously determined to have 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. The biopsy must have been obtained at or after the diagnosis of advanced disease
  • Unstained tumor tissue (in a quantity sufficient to allow for central analysis of epidermal growth factor receptor (EGFR) mutation status, see Laboratory Manual) and blood (for circulating tumor deoxyribonucleic acid [ctDNA], digital droplet polymerase chain reaction [ddPCR], and pharmacogenomic analysis), both collected at or after the diagnosis of locally advanced or metastatic NSCLC, must be provided
  • 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 for locally advanced or metastatic disease (adjuvant or neoadjuvant therapy 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 has spinal cord compression that has not been definitively treated with surgery or radiation or requires steroid treatment within 2 weeks prior to randomization
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04487080


Contacts
Layout table for location contacts
Contact: Study Contact 844-434-4210 JNJ.CT@sylogent.com

Locations
Show Show 264 study locations
Sponsors and Collaborators
Janssen Research & Development, LLC
Investigators
Layout table for investigator information
Study Director: Janssen Research & Development, LLC Clinical Trial Janssen Research & Development, LLC
Additional Information:
Layout table for additonal information
Responsible Party: Janssen Research & Development, LLC
ClinicalTrials.gov Identifier: NCT04487080    
Other Study ID Numbers: CR108856
2020-000743-31 ( EudraCT Number )
73841937NSC3003 ( Other Identifier: Janssen Research & Development, LLC )
First Posted: July 27, 2020    Key Record Dates
Last Update Posted: October 19, 2020
Last Verified: October 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson and Johnson is available at www.janssen.com/clinical- trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) project site at yoda.yale.edu
URL: https://www.janssen.com/clinical-trials/transparency

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Osimertinib
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action