Carcinoma, Non-small-Cell Lung
Conditions
Brief summary
The purpose of this study is to assess the anti-tumor activity and safety of amivantamab which will be administered as a co-formulation with recombinant human hyaluronidase PH20 (rHuPH20) (subcutaneous co-formulation \[SC-CF\]) in combination treatment (all cohorts except Cohort 4) and to characterize the safety of amivantamab SC-CF (Cohort 4).
Interventions
LMWH will be administered subcutaneously.
DRUGAmivantamab
Amivantamab will be administered subcutaneously by manual injection.
DRUGLazertinib
Lazertinib will be administered as an oral tablet.
DRUGCarboplatin
Carboplatin will be administrated by IV infusion.
DRUGPemetrexed
Pemetrexed will be administered by IV infusion.
DOAC will be administered orally.
Sponsors
Janssen Research & Development, LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-small cell lung cancer (NSCLC) that is not amenable to curative therapy including surgical resection or chemoradiation. Additional Cohort specific disease requirements include: Cohorts 1, 3, 3b, 5, 6 and 7: epidermal growth factor receptor (EGFR) exon 19 deletion (Exon19del) or Exon 21 L858R mutation; Cohort 2: EGFR Exon 20ins mutation. Cohorts 1,5,and6: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohort 2: Participant should not have received any prior systemic therapy for locally advanced or metastatic NSCLC. Cohorts 3and3b: 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. Cohort 4: Participants need to currently be on an amivantamab IV Q2W regimen (1,050 mg or 1,400 mg depending on weight) for at least 8 weeks, as part of standard of care, an expanded access program, or as a rollover from a long-term extension, without any amivantamab dose reduction. Cohort 7: Participants must have progressed on or after the combination of amivantamab and lazertinib as the most recent line of treatment. The combination of amivantamab and lazertinib must have been administered as the first-line treatment for locally advanced or metastatic disease. Cohort 2, 3, 3b, and 7 only: Squamous NSCLC are excluded. EGFR mutation must have been identified as determined by Food and Drug Administration (FDA) approved or other validated test of either circulating tumor deoxyribonucleic acid (ctDNA) or tumor tissue 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). A copy of the initial test report documenting the EGFR mutation must be included in the participant records and a deidentified copy must also be submitted to the sponsor * All cohorts except Cohort 4: Participants must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. If the only target lesion has been previously irradiated, it must show signs of disease progression since radiation was completed If only 1 non-irradiated measurable lesion exists, which undergoes a biopsy and is acceptable as a target lesion, the baseline tumor assessment scans should be performed at least 14 days after the biopsy * May have a prior or concurrent second malignancy (other than the disease under study) which natural history or treatment is unlikely to interfere with any study endpoints of safety or the efficacy of the study treatment(s) * Have adequate organ (renal, hepatic, hematological, coagulation and cardiac) functions * Participant must have eastern cooperative oncology group (ECOG) status of 0 or 1 * Cohort 6: Must be eligible for, and agree to comply with, the use of prophylactic anticoagulation with a direct oral anticoagulant or a low molecular weight heparin during the first 4 months of study treatment * A participant must agree not to donate eggs (ova, oocytes) or freeze for future use for the purposes of assisted reproduction during the study and for a period of 6 months after receiving the last dose of study treatment. Participants with child bearing potential should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility
Exclusion criteria
* Participant has a medical history of interstitial lung disease (ILD), including drug induced ILD or radiation pneumonitis * Participant has a history of hypersensitivity to any excipients of the investigational products to be used in their enrollment cohort * Participant has received a live or live attenuated vaccine within 3 months before Cycle 1 Day 1. The seasonal influenza vaccine and non-live vaccines against Coronavirus disease 19 (COVID-19) are not exclusionary * For all cohorts (with regimens potentially including lazertinib): Participant is currently receiving medications or herbal supplements known to be potent Cytochrome (CYP3A4/5) inducers and is unable to stop use for an appropriate washout period prior to Cycle 1 Day 1 * Other clinically active liver disease of infectious origin * Participant has a history of clinically significant cardiovascular disease including, but not limited to: a) All cohorts: diagnosis of deep vein thrombosis or pulmonary embolism within 1 month prior to the first dose of study treatment(s), or any of the following within 6 months prior to the first dose of study treatment(s): myocardial infarction, unstable angina, stroke, transient ischemic attack, coronary/peripheral artery bypass graft, or any acute coronary syndrome. Clinically non-significant thrombosis, such as non-obstructive catheter-associated clots, are not exclusionary; b) All cohorts (with regimens potentially including lazertinib): Participant has a significant genetic predisposition to venous thromboembolic events (VTE; such as Factor V Leiden); c) All cohorts (with regimens potentially including lazertinib): Participant has a prior history of VTE and is not on appropriate therapeutic anticoagulation as per NCCN or local guidelines; d) prolonged corrected QT interval by Fridericia (QTcF) interval greater than (\>) 480 milliseconds (msec) or clinically significant cardiac arrhythmia or electrophysiologic disease (example, placement of implantable cardioverter defibrillator or atrial fibrillation with uncontrolled rate); e) uncontrolled (persistent) hypertension: systolic blood pressure \>160 millimeter(s) of mercury (mmHg); diastolic blood pressure \>100 mmHg; f) Congestive heart failure defined as NYHA class III-IV or hospitalization for congestive heart failure (CHF) (any New York Heart Association \[NYHA\] class) within 6 months of treatment initiation at Cycle 1/day 1 (C1D1); g) pericarditis/clinically significant pericardial effusion; h) myocarditis; i) baseline left ventricular ejection fraction (LVEF) below the institution's lower limit of normal at screening, as assessed by echocardiogram or multigated acquisition (MUGA) scan * Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have received definitive radiation or surgical treatment for symptomatic or unstable brain metastases and have been clinically stable and asymptomatic for at least 2 weeks before Screening are eligible, provided they have been either off corticosteroid treatment or are receiving low-dose corticosteroid treatment (less than or equal to \[\<=\] 10 milligrams per day \[mg/day\] prednisone or equivalent) for at least 2 weeks prior to treatment allocation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts Except Cohort 4: Objective Response Rate (ORR) Based on Investigator Assessment (INV) | Up to 1 year 6 months | ORR based on INV will be reported. ORR is defined as the percentage of participants who achieve a complete response (CR) or partial response (PR), based on Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, as determined by investigator. |
| Cohort 4: Number of Participants with Adverse Events (AEs) | Up to approximately 4 years and 9 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. |
| Cohort 4: Number of Participants with AEs by Severity | Up to approximately 4 years and 9 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values | Up to approximately 4 years and 9 months | Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported. |
| Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity | Up to approximately 4 years and 9 months | Number of participants with laboratory values abnormalities which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the NCI-CTCAE version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| All Cohorts Except Cohort 4: Number of Participants with AEs | Up to 1 year 6 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. |
| All Cohorts Except Cohort 4: Number of Participants with AEs by Severity | Up to 1 year 6 months | An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values | Up to 1 year 6 months | Number of participants with abnormalities in clinical laboratory values (which includes serum chemistry, hematology, coagulation, urinalysis, and serology) will be reported. |
| All Cohorts Except Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity | Up to 1 year 6 months | Number of participants with abnormalities in clinical laboratory values which includes serum chemistry, hematology, coagulation, urinalysis, and serology) by severity will be reported. Severity of laboratory values abnormalities will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). Grade 1= Mild, Grade 2= Moderate, Grade 3= Severe, Grade 4= Life-threatening and Grade 5= Death related to adverse event. |
| All Cohorts Except Cohort 4: ORR Based on Independent Central Review (ICR) | Up to 1 year 6 months | ORR based on ICR will be reported. The ORR is defined as the percentage of participants who achieve a CR or PR, based on RECIST version 1.1, as confirmed by ICR. |
| All Cohorts Except Cohort 4: Duration of Response (DoR) Based on Investigator Assessment (INV) | Up to 1 year 6 months | DoR based on INV is defined as the time from the date of first documented response (PR or CR) until the date of documented progression or death, whichever comes first, for participants who have PR or CR. |
| All Cohorts Except Cohort 4: Time to Response (TTR) Based on INV | Up to 1 year 6 months | TTR (that is, time to first response) based on INV is defined as the time from the first dose of study treatment to the date of first documentation of a response (PR or CR) prior to any disease progression and subsequent anticancer therapy, based on RECIST version 1.1., for participants who have PR or CR as their best response. |
| All Cohorts Except Cohort 4: Clinical Benefit Rate (CBR) | Up to 1 year 6 months | CBR is defined as the percentage of participants achieving CR or PR, or durable standard deviation (SD) of a duration of at least 11 weeks as defined by RECIST version 1.1. |
| All Cohorts Except Cohort 4: Progression-free Survival (PFS) | Up to 3 years | The PFS is defined as the time from the first dose of study treatment until the date of objective disease progression or death, whichever comes first, based on RECIST version 1.1. |
| All Cohorts Except Cohort 4: Overall Survival (OS) | Up to approximately 4 years | The OS is defined as the time from the first dose of study treatment until the date of death due to any cause. |
| All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) | Up to 1 year 6 months | Number of participants with adverse events of VTE (pulmonary embolism and deep vein thrombosis) will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. |
| All Cohorts Except Cohort 4: Number of Participants with Venous Thromboembolic Events (VTE) by Severity | Up to 1 year 6 months | Number of participants with adverse events of VTE (pulmonary embolism and deep vein thrombosis) by severity will be reported. An AE is any untoward medical occurrence in a participant participating in a clinical study that does not necessarily have a causal relationship with the pharmaceutical/ biological agent under study. Severity of AEs will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 5.0. Severity scale ranges from Grade 1 (Mild) to Grade 5 (Death). |
| All Cohorts Except Cohort 4: Serum Concentration Immediately Prior to the Next Dose Administration (Ctrough) of Amivantamab | Cycle 2 Day 1 of 28-day cycle | Ctrough is defined as the serum concentration of amivantamab immediately prior to the next drug administration. |
| Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Intravenous (TASQ-IV) | Up to 1 year 6 months | Patient-reported outcome (PRO): Cancer therapy satisfaction will be assessed using the modified TASQ-IV. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best. |
| Cohort 4: Cancer Therapy Satisfaction as Assessed by Modified Therapy Administration Satisfaction Questionnaire - Subcutaneous (TASQ-SC) | Up to 1 year 6 months | PRO: Cancer therapy satisfaction will be assessed using the modified TASQ-SC. The modified TASQ is a 12-item questionnaire measuring the impact of each mode of treatment administration on five domains: physical impact, psychological impact, impact on activities of daily living, convenience, and satisfaction. Each of the domain/scale scores is scored on a 1-100 scale, where 0 is worst and 100 is best. |
| Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Change (PGIC) Scale Score | Up to 1 year 6 months | Patient-reported status as assessed by PGIC scale score will be reported. The PGIC is an assessment of the participant's overall sense of whether there has been a change since starting treatment. The PGIC is a 7-point response scale. Participants will be asked to rate their current fatigue as compared to when they started the study, using the following 7-point scale: 1 = Much better, 2 = Moderately better, 3 = A little better, 4 = No change, 5 = A little worse, 6 = Moderately worse, and 7 = Much worse. |
| Cohort 4: Patient-reported Status as Assessed by Patient Global Impression of Symptom Severity (PGIS) Scale Score | Up to 1 year 6 months | Patient-reported status as assessed by PGIS scale score will be reported. The PGIS is an assessment of lung cancer severity at a given point in time. The PGIS is a 5-point response scale. Participants will be asked to rate their fatigue over the past 7 days using the following 5-point scale: 1 = None, 2 = Mild, 3 = Moderate, 4 = Severe, and 5 = Very severe. |
Countries
Brazil, China, France, Germany, Israel, Italy, Japan, Malaysia, South Korea, Spain, United Kingdom, United States
Contacts
CONTACTStudy Contact
STUDY_DIRECTORJanssen Research & Development, LLC Clinical Trial
Janssen Research & Development, LLC
Outcome results
None listed