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

NCT04487080

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • 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.

Clinical Trial IDs

  • ORG STUDY ID: CR108856
  • SECONDARY ID: 2020-000743-31
  • SECONDARY ID: 73841937NSC3003
  • NCT ID: NCT04487080

Conditions

  • Carcinoma, Non-Small-Cell Lung

Interventions

DrugSynonymsArms
AmivantamabJNJ-61186372Treatment Arm A (Open-label): Amivantamab and Lazertinib
OsimertinibTreatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib
LazertinibJNJ-73841937 and YH-25448Treatment Arm A (Open-label): Amivantamab and Lazertinib
PlaceboTreatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib

Purpose

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).
    

Trial Arms

NameTypeDescriptionInterventions
Treatment Arm A (Open-label): Amivantamab and LazertinibExperimentalParticipants 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.
  • Amivantamab
  • Lazertinib
Treatment Arm B (Double-blind): Osimertinib+Placebo LazertinibActive ComparatorParticipants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80*3) orally once daily.
  • Osimertinib
  • Placebo
Treatment Arm C (Double-blind): Lazertinib+Placebo OsimertinibExperimentalParticipants will receive lazertinib 240 mg (80*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily.
  • Lazertinib
  • Placebo

Eligibility 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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Progression-Free Survival (PFS) According to RECIST v1.1 by Blinded Independent Central Review (BICR)
Time Frame:Up to approximately 42 months
Safety Issue:
Description: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

Measure: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)
Safety Issue:
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:Objective Response Rate (ORR)
Time Frame:Up to approximately 42 months
Safety Issue:
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:Duration of Response (DOR)
Time Frame:Up to approximately 42 months
Safety Issue:
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:Progression-Free Survival After First Subsequent Therapy (PFS2)
Time Frame:Up to approximately 42 months
Safety Issue:
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:Time to Symptomatic Progression (TTSP)
Time Frame:Up to approximately 42 months
Safety Issue:
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:Intracranial PFS
Time Frame:Up to approximately 42 months
Safety Issue:
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:Incidence and Severity of Adverse Events (AEs)
Time Frame:Up to approximately 60 months
Safety Issue:
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:Number of Participants with Clinical Laboratory Abnormalities
Time Frame:Up to approximately 60 months
Safety Issue:
Description:Number of participants with clinical laboratory abnormalities (serum chemistry, hematology, blood coagulation, and urine samples) will be reported.
Measure:Number of Participants with Vital Signs Abnormalities
Time Frame:Up to approximately 60 months
Safety Issue:
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 Physical Examination Abnormalities
Time Frame:Up to approximately 60 months
Safety Issue:
Description:Number of participants with physical examination abnormalities will be reported.
Measure:Serum Concentration of Amivantamab
Time Frame:Up to approximately 42 months
Safety Issue:
Description:Serum samples will be analyzed to determine concentrations of amivantamab.
Measure:Plasma Concentration of Lazertinib
Time Frame:Up to approximately 42 months
Safety Issue:
Description:Plasma samples will be analyzed to determine concentrations of lazertinib.
Measure:Number of Participants with Anti-Amivantamab Antibodies
Time Frame:Up to approximately 42 months
Safety Issue:
Description:Number of participants with antibodies to amivantamab will be reported.
Measure:Change from Baseline in Non-Small Cell Lung Cancer - Symptom Assessment Questionnaire (NCSLC-SAQ)
Time Frame:Baseline Up to approximately 42 months
Safety Issue:
Description: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.
Measure: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
Safety Issue:
Description: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.

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

July 23, 2020