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).
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
Drug | Synonyms | Arms |
---|
Amivantamab | JNJ-61186372 | Treatment Arm A (Open-label): Amivantamab and Lazertinib |
Osimertinib | | Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib |
Lazertinib | JNJ-73841937 and YH-25448 | Treatment Arm A (Open-label): Amivantamab and Lazertinib |
Placebo | | Treatment 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
Name | Type | Description | Interventions |
---|
Treatment Arm A (Open-label): Amivantamab and Lazertinib | Experimental | 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. | |
Treatment Arm B (Double-blind): Osimertinib+Placebo Lazertinib | Active Comparator | Participants will receive osimertinib 80 mg orally once daily plus matching placebo of lazertinib 240 mg (80*3) orally once daily. | |
Treatment Arm C (Double-blind): Lazertinib+Placebo Osimertinib | Experimental | Participants will receive lazertinib 240 mg (80*3) orally once daily plus matching placebo of osimertinib 80 mg orally once daily. | |
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 for locally advanced or
metastatic disease (adjuvant or neoadjuvant therapy for early stage 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
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: | Recruiting |
Lead Sponsor: | Janssen Research & Development, LLC |
Last Updated
August 20, 2021