Premedication to Reduce Amivantamab Associated Infusion Related Reactions

• ClinicalTrials.gov Identifier: NCT05663866
• Recruitment Status: Active, not recruiting
• First Posted: December 23, 2022
• Last Update Posted: April 24, 2024
• Sponsor: Janssen Research & Development, LLC
• Information provided by (Responsible Party): Janssen Research & Development, LLC

Tracking Information

• First Submitted Date: December 16, 2022
• First Posted Date: December 23, 2022
• Last Update Posted Date: April 24, 2024
• Actual Study Start Date: May 18, 2023
• Estimated Primary Completion Date: December 15, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2023)

Percentage of Participants with Infusion-related Reactions (IRRs) [ Time Frame: Cycle 1 Day 1 ]

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.

Original Primary Outcome Measures (submitted: December 16, 2022)

Percentage of Participants with Infusion-related Reactions (IRRs) [ Time Frame: Cycle 1 Day 1 ]

Percentage of participants with IRRs will be reported.

Current Secondary Outcome Measures (submitted: June 1, 2023)

• Percentage of Participants with Adverse Events (AEs) of Infusion-related Reactions (IRRs) at Cycle 1 Day 1 [ Time Frame: 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.
• Percentage of Participants with Adverse Events (AEs) of IRR by Severity at Cycle 1 Day 1 [ Time Frame: 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.
• Percentage of Participants with Adverse Events (AEs) of IRRs up to End of the Cycle 3 [ Time Frame: Up to end of the Cycle 3 (Each Cycle 28 days) ]
  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.
• Percentage of Participants with Adverse Events (AEs) of IRRs by Severity up to End of the Cycle 3 [ Time Frame: Up to end of the Cycle 3 (Each Cycle 28 days) ]
  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.
• Percentage of Participants with IRRs [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  Percentage of participants with IRRs will be reported.
• Percentage of Participants with IRR by Severity [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  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.
• Percentage of Participants with Other Adverse Events (AEs) [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  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.
• Duration of Infusion Time for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1 [ Time Frame: 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.
• Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1 [ Time Frame: 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.
• Overall Response Rate (ORR) [ Time Frame: Up to 14 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 14 months ]
  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.

Original Secondary Outcome Measures (submitted: December 16, 2022)

• Percentage of Participants with Adverse Events (AEs) of Infusion-related Reactions (IRRs) at Cycle 1 Day 1 [ Time Frame: 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/biological agent under study.
• Percentage of Participants with Adverse Events (AEs) of IRR by Severity at Cycle 1 Day 1 [ Time Frame: 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/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.
• Percentage of Participants with Adverse Events (AEs) of IRRs up to 3 Months [ Time Frame: Up to 3 months ]
  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.
• Percentage of Participants with Adverse Events (AEs) of IRRs by Severity up to 3 Months [ Time Frame: Up to 3 months ]
  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 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.
• Percentage of Participants with IRRs [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  Percentage of participants with IRRs will be reported.
• Percentage of Participants with IRR by Severity [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  Percentage of participants with IRR by severity will be reported. 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.
• Percentage of Participants with Other Adverse Events (AEs) [ Time Frame: Up to 30 days after end of treatment (14 months) ]
  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.
• Time to Complete Infusion for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1 [ Time Frame: Cycle 1 Day 1 ]
  Time to complete infusion for pre-amivantamab infusion medications, intravenous (IV) amivantamab infusion, and post-amivantamab infusion medications on Cycle 1 Day 1 will be reported.
• Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1 [ Time Frame: 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.
• Overall Response Rate (ORR) [ Time Frame: Up to 14 months ]
  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.
• Duration of Response (DOR) [ Time Frame: Up to 14 months ]
  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.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Premedication to Reduce Amivantamab Associated Infusion Related Reactions
• Official Title: 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
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Carcinoma, Non-Small-Cell Lung

Intervention

• Drug: Dexamethasone
  Dexamethasone will be administered orally.
• Drug: Montelukast
  Montelukast will be administered orally.
• Drug: Methotrexate
  Methotrexate will be administered subcutaneously.
• Drug: Amivantamab
  Amivantamab will be administered intravenously.
  Other Name: JNJ-61186372
• Drug: Lazertinib
  Lazertinib tablets will be administered orally.
  Other Name: JNJ-73841937

Study Arms

Experimental: Background Anti-cancer Therapy with Amivantamab Plus Lazertinib

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.

Interventions:

• Drug: Dexamethasone
• Drug: Montelukast
• Drug: Methotrexate
• Drug: Amivantamab
• Drug: Lazertinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 23, 2024): 74
• Original Estimated Enrollment (submitted: December 16, 2022): 120
• Estimated Study Completion Date: August 31, 2026
• Estimated Primary Completion Date: December 15, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: France, Korea, Republic of, Spain, Taiwan, United States

Administrative Information

• NCT Number: NCT05663866
• Other Study ID Numbers: CR109305; 2022-000974-25 ( EudraCT Number ); 61186372NSC2005 ( Other Identifier: Janssen Research & Development, LLC ); 2023-506578-11-00 ( Registry Identifier: EUCT number )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: The data sharing policy of the Janssen Pharmaceutical Companies of Johnson & Johnson is available at www.janssen.com/clinical-trials/transparency. As noted on this site, requests for access to the study data can be submitted through Yale Open Data Access (YODA) Project site at yoda.yale.edu
• URL: https://www.janssen.com/clinical-trials/transparency

• Current Responsible Party: Janssen Research & Development, LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Janssen Research & Development, LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Janssen Research & Development, LLC Clinical Trial; Janssen Research & Development, LLC

• PRS Account: Janssen Research & Development, LLC
• Verification Date: April 2024