Premedication to Reduce Amivantamab Associated Infusion Related Reactions

Study Overview
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Brief Summary
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The purpose of the study is to separately assess the potential of dexamethasone, montelukast and methotrexate administration, prior to amivantamab infusion given through a needle in the vein, to decrease the incidence and/or severity of first-dose infusion related reactions.

Official Title
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Subcutaneous Methotrexate, Oral Dexamethasone or Oral Montelukast for the Prevention of Infusion Related Reaction Associated With Amivantamab, an EGFR-MET Bispecific Antibody, Among Post-osimertinib Treated EGFRm NSCLC; SKIPPirr, a Phase 2 Study

Conditions
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Carcinoma, Non-Small-Cell Lung

Intervention / Treatment
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* Drug: Dexamethasone
* Drug: Montelukast
* Drug: Methotrexate
* Drug: Amivantamab
* Drug: Lazertinib


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Participant must have advanced or metastatic non-small cell lung cancer (NSCLC) Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1 A female participant using oral contraceptives must use an additional barrier contraceptive method A male participant must wear a condom when engaging in any activity that allows for passage of ejaculate to another person during the study and for 3 months after receiving the last dose of study treatment, oral lazertinib and intravenous (IV) Amivantamab Each participant, or legally authorized representative, where allowed, must sign an informed consent form (ICF) indicating that the participant understands the purpose of, and procedures required for, the study and is willing to participate in the study Progressed on or after prior treatment with osimertinib and platinum-based chemotherapy. Prior use of first-or-second generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) is allowed if administered prior to osimertinib Previously identified EGFR-mutated non-small cell lung cancer (NSCLC) (EGFR Exon19 deletion or L858R) (identified locally in a Clinical Laboratory Improvement Amendments [CLIA]-certified laboratory [or equivalent]) Exclusion Criteria: Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis Prior treatment with anti PD-1 or anti PD-L1 antibody within 6 weeks of planned first dose of study treatment or immune-mediated rash from checkpoint inhibitors that has not resolved prior to enrollment Participant has symptomatic brain metastases. A participant with asymptomatic or previously treated and stable brain metastases may participate in this study. Participants who have completed definitive therapy, are not on steroids, and have a stable clinical status for at least 2 weeks prior to study treatment are allowed. If brain metastases are diagnosed on Screening imaging, the participant may be enrolled, or rescreened for eligibility, after definitive treatment if above criteria are met Any toxicities from prior anticancer therapy must have resolved to common terminology criteria for adverse events (CTCAE) version 5.0 Grade 1 or baseline level (except for alopecia [any grade], Grade less than or equal to [<=] 2 peripheral neuropathy, and Grade <=2 hypothyroidism stable on hormone replacement therapy) Prior treatment with amivantamab or lazertinib

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Background Anti-cancer Therapy with Amivantamab Plus Lazertinib<br>Participant will receive following treatments in 4 different cohorts prior to administration of combination therapy of IV Amivantamab and oral Lazertinib (anti-cancer regimen): dexamethasone dose-1 in Cohort A; dexamethasone dose-2 in Cohort A2; montelukast in Cohort B; and methotrexate in Cohort C. | Drug: Dexamethasone<br>* Dexamethasone will be administered orally.<br>Drug: Montelukast<br>* Montelukast will be administered orally.<br>Drug: Methotrexate<br>* Methotrexate will be administered subcutaneously.<br>Drug: Amivantamab<br>* Amivantamab will be administered intravenously.<br>* Other names: JNJ-61186372;Drug: Lazertinib<br>* Lazertinib tablets will be administered orally.<br>* Other names: JNJ-73841937;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Infusion-related Reactions (IRRs) | Percentage of participants with IRRs events with onset time within 24 hours of the start of the first amivantamab infusion and prior to the start of amivantamab infusion on Cycle 1 Day 2 will be reported. | Cycle 1 Day 1 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants with Adverse Events (AEs) of Infusion-related Reactions (IRRs) at Cycle 1 Day 1 | Percentage of participants with AEs of chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever 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 or biological agent under study. | Cycle 1 Day 1 | 
| Percentage of Participants with Adverse Events (AEs) of IRR by Severity at Cycle 1 Day 1 | Percentage of participants with AEs of chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever by severity at Cycle 1 Day 1 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 or biological agent under study. Severity 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. | Cycle 1 Day 1 | 
| Percentage of Participants with Adverse Events (AEs) of IRRs up to End of the Cycle 3 | Percentage of participants with AEs of chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever 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. | Up to end of the Cycle 3 (Each Cycle 28 days) | 
| Percentage of Participants with Adverse Events (AEs) of IRRs by Severity up to End of the Cycle 3 | Percentage of participants with AEs of chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever 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 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. | Up to end of the Cycle 3 (Each Cycle 28 days) | 
| Percentage of Participants with IRRs | Percentage of participants with IRRs will be reported. | Up to 30 days after end of treatment (14 months) | 
| Percentage of Participants with IRR by Severity | Percentage of participants with IRR by severity will be reported. Severity 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. | Up to 30 days after end of treatment (14 months) | 
| Percentage of Participants with Other Adverse Events (AEs) | Other 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 and which is not a serious adverse event. | Up to 30 days after end of treatment (14 months) | 
| Duration of Infusion Time for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1 | Duration of infusion time for pre-amivantamab infusion medications, intravenous (IV) amivantamab infusion, and post-amivantamab infusion medications on Cycle 1 Day 1 will be reported. | Cycle 1 Day 1 | 
| Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1 | Percentage of participants completing amivantamab infusion within 4 hours on Cycle 1 Day 1 will be reported. | Within 4 hours on Cycle 1 Day 1 | 
| Overall Response Rate (ORR) | ORR is defined as the percentage of participants who achieve either a complete (CR) or partial response (PR) as defined by investigator assessment using response criteria in solid tumors (RECIST) Version 1.1. | Up to 14 months | 
| Duration of Response (DOR) | DOR is defined as time from initial response of CR or PR to progressive disease (PD) or death due to underlying disease, whichever comes first, only for participants who achieve CR or PR as defined by investigator assessment using response criteria in solid tumors (RECIST) Version 1.1. | Up to 14 months |