A Study of Amivantamab in Participants with Advanced or Metastatic Solid Tumors including Epidermal Growth Factor Receptor (EGFR)-mutated Non-Small Cell Lung Cancer

JRCT ID: jRCT2051220116

Registered date:17/11/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Carcinoma, Non-small-Cell Lung
• Date of first enrollment: 02/10/2023
• Target sample size: 390
• Countries of recruitment: Brazil,Japan,China,Japan,Spain,Japan,Germany,Japan,France,Japan,United Kingdom,Japan,Israel,Japan,Italy,Japan,Korea,Japan,Malaysia,Japan,United States,Japan
• Study type: Interventional

Intervention(s)

Cohort 1(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q2W) + Lazertinib
Participants will receive amivantamab SC-CF injection, 1600 milligrams (mg) or 2240 mg if body weight is greater than or equal to (>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily.

Cohort 2(Exon20 NSCLC,1L, Previously Untreated): Amivantamab (Q3W) + Chemotherapy
Participants will receive Amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle, starting with Cycle 2 along with pemetrexed 500 milligrams per meter square (mg/m^2) as intravenous (IV) infusion (with vitamin supplementation) on Day 1 of each 21-day cycle and IV infusion carboplatin area under the concentration-time curve 5 milligrams per milliliters (mg/mL) per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles.

Cohort 3(Exon19del/Exon21 L858R NSCLC,2L,Post Osimertinib):Amivantamab(Q3W)+Lazertinib+Chemotherapy
Participants will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression. Lazertinib 240 mg orally once daily starting Cycle 5 Day 1 when carboplatin is complete or sooner if carboplatin discontinued earlier than Cycle 4.

Cohort 3b(Exon19del/Exon21 L858R NSCLC, 2L, Post Osimertinib): Amivantamab (Q3W)+Chemotherapy
Participants will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.

Cohort 4(Previously Treated with Amivantamab IV): Switch from Amivantamab IV to SC-CF (Q2W)
Participants will receive amivantamab SC-CF injection 1600 mg and 2240 mg if body weight is greater than or equal to 80 kg.

Cohort 5(Exon19del/Exon21 L858R NSCLC, 1L, Previously Untreated): Amivantamab (Q4W) + Lazertinib
Participants will receive amivantamab SC-CF induction with 1,600 mg (or 2,240 mg if BW >=80 kg) on Cycle 1 Days 1, 8, 15, and 22, starting with Cycle 2 on Day 1 of each next 28-day cycle, amivantamab SC-CF (160 mg/mL co-formulated with rHuPH20) by manual injection at 3,520 mg (or 4,640 mg if BW >=80 kg); along with lazertinib 240 mg by mouth once daily from Cycle 1 Day 1.

Cohort6(Exon19del/Exon21L858R,NSCLC1L,PreviouslyUntreated):Amivantamab(Q2W)+Lazertinib+Anticoagulant
Participants will receive will receive amivantamab SC-CF injection, 1600 milligrams (mg) and 2240 mg if body weight is greater than or equal to (>=) 80 kilograms (kg), on Cycle 1 Days 1, 8, 15, and 22 and on Days 1 and 15 of each subsequent 28-day cycle, starting with Cycle 2, along with lazertinib 240 mg orally once daily from Cycle 1 Day 1. Participants will additionally take prophylactic anticoagulation with a direct oral anticoagulant (DOAC) or a low molecular weight heparin (LMWH) for the first four months of study treatment (from Day 1 through Day 120) with the combination of amivantamab and lazertinib.

Cohort 7(Exon19del/Exon21 L858R NSCLC,2L,Post Amivantamab+Lazertinib):Amivantamab(Q3W)+Chemotherapy
Participants will receive amivantamab SC-CF injection 1600 mg or 2240 mg if body weight is >=80 kg on Cycle 1 Day 1, 2400 mg or 3360 mg if body weight is >=80 kg on Cycle 1 Day 8 and 15 and on Day 1 of each subsequent 21-day cycle starting with Cycle 2; in combination with IV infusion carboplatin area under the concentration-time curve 5 mg/mL per minute (AUC 5) maximum 750 mg on Day 1 of each 21-day cycle, for up to 4 cycles; and pemetrexed 500 mg/m^2 as an IV infusion (with vitamin supplementation) on Day 1 of each 21-day until disease progression.

Amivantamab will be administered subcutaneously by manual injection.
Lazertinib will be administered as an oral tablet.
Carboplatin will be administrated by IV infusion.
Pemetrexed will be administered by IV infusion.
Direct Oral Anticoagulant (DOAC) will be administered orally.
Low Molecular Weight Heparin (LMWH) will be administered subcutaneously.

Outcome(s)

Primary Outcome

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 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.

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.

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.

Cohort 4: Number of Participants with Abnormalities in Clinical Laboratory Values by Severity
Up to 1 year 6 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 Outcome

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 1 year 6 months
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 1 year 6 months
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.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include 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 longterm 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. Female participants should consider preservation of eggs prior to study treatment as anti-cancer treatments may impair fertility

Exclude 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

Related Information

• Primary Sponsor: Nakama Takahiro
• Secondary ID(s): NCT05498428,2022-000526-21