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

• ClinicalTrials.gov Identifier: NCT04487080
• Recruitment Status: Active, not recruiting
• First Posted: July 27, 2020
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: July 23, 2020
• First Posted Date: July 27, 2020
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: September 30, 2020
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 27, 2021)

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 occurred first, based on BICR using response evaluation criteria in solid tumors (RECIST) v1.1.

Original Primary Outcome Measures (submitted: July 23, 2020)

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.

Current Secondary Outcome Measures (submitted: July 23, 2020)

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• 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.
• Number of Participants with Physical Examination Abnormalities [ Time Frame: Up to approximately 60 months ]
  Number of participants with physical examination abnormalities will be reported.
• Serum Concentration of Amivantamab [ Time Frame: Up to approximately 42 months ]
  Serum samples will be analyzed to determine concentrations of amivantamab.
• Plasma Concentration of Lazertinib [ Time Frame: Up to approximately 42 months ]
  Plasma samples will be analyzed to determine concentrations of lazertinib.
• Number of Participants with Anti-Amivantamab Antibodies [ Time Frame: Up to approximately 42 months ]
  Number of participants with antibodies to amivantamab will be reported.
• 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.
• 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.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer
• 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.
• 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).
• 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).
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Amivantamab
  Participants will receive amivantamab intravenously.
  Other Name: JNJ-61186372
• Drug: Osimertinib
  Participants will receive osimertinib capsules orally.
• Drug: Lazertinib
  Participants will receive lazertinib tablets orally.
  Other Name: JNJ-73841937 and YH-25448
• Drug: Placebo
  Participants will receive matching placebo orally.

Study Arms

• 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.
  Interventions:

  • Drug: Amivantamab
  • Drug: Lazertinib
• 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.
  Interventions:

  • Drug: Osimertinib
  • Drug: Placebo
• 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.
  Interventions:

  • Drug: Lazertinib
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 16, 2022): 1074
• Original Estimated Enrollment (submitted: July 23, 2020): 1000
• Estimated Study Completion Date: June 9, 2027
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Argentina, Australia, Belgium, Brazil, Canada, China, France, Germany, Hungary, India, Israel, Italy, Japan, Korea, Republic of, Malaysia, Mexico, Netherlands, Poland, Portugal, Puerto Rico, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine, United Kingdom, United States

Administrative Information

• NCT Number: NCT04487080
• Other Study ID Numbers: CR108856; 2020-000743-31 ( EudraCT Number ); 73841937NSC3003 ( Other Identifier: Janssen Research & Development, LLC )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024