Premedication to Reduce Amivantamab Associated Infusion Related Reactions

Carcinoma, Non-Small-Cell Lung Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05663866
• Other study ID #: CR109305
• Secondary ID: 2022-000974-2561
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: May 18, 2023
• Est. completion date: August 31, 2026

Study information

• Verified date: June 2024
• Source: Janssen Research & Development, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 74
• Est. completion date: August 31, 2026
• Est. primary completion date: December 15, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung

Intervention

Drug:
• Dexamethasone
Dexamethasone will be administered orally.
• Montelukast
Montelukast will be administered orally.
• Methotrexate
Methotrexate will be administered subcutaneously.
• Amivantamab
Amivantamab will be administered intravenously.
• Lazertinib
Lazertinib tablets will be administered orally.

Locations

Country	Name	City	State
France	CHU Brest	Brest
France	Centre Leon Berard	Lyon Cedex 8
France	Hopital Cochin	Paris
France	Hopital Europeen Georges-Pompidou	Paris
France	CHU Rouen Hopital Charles Nicolle	Rouen
France	Nouvel Hopital Civil - CHU Strasbourg	Strasbourg CEDEX
Korea, Republic of	Chungbuk National University Hospital	Cheongju-si
Korea, Republic of	National Cancer Center	Gyeonggi-do
Korea, Republic of	Seoul National University Bundang Hospital	Gyeonggi-do
Korea, Republic of	Gachon University Gil Medical Center	Incheon
Korea, Republic of	Chonnam National University Hwasun Hospital	Jeollanam-do
Korea, Republic of	Asan Medical Center	Seoul
Spain	Hosp. de La Santa Creu I Sant Pau	Barcelona
Spain	Hosp. Univ. Quiron Dexeus	Barcelona
Spain	Hosp. Univ. Vall D Hebron	Barcelona
Spain	Hosp. San Pedro de Alcantara	Cáceres
Spain	Hosp. de Jerez de La Frontera	Jerez de la Frontera
Spain	Inst. Cat. Doncologia-H Duran I Reynals	L Hospitalet De Llobregat
Spain	Hosp. Gral. Univ. Gregorio Maranon	Madrid
Spain	Hosp. Univ. 12 de Octubre	Madrid
Spain	Hosp. Virgen de La Victoria	Malaga
Spain	Hosp. Univ. Son Espases	Palma de Mallorca
Spain	Hosp. Clinico Univ. de Santiago	Santiago de Compostela
Spain	Hosp. Gral. Univ. Valencia	Valencia
Spain	Inst. Valenciano de Oncologia	Valencia
Spain	Hosp. Clinico Univ. Lozano Blesa	Zaragoza
Taiwan	Changhua Christian Hospital	ChangHua
Taiwan	Kaohsiung Medical University Chung-Ho Memorial Hospital	Kaohsiung
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Chi-Mei Medical Center, Liouying	Tainan City
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei Veterans General Hospital	Taipei
Taiwan	Taipei Medical University	Taipei City
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	Compassionate Cancer Care	Fountain Valley	California
United States	UW Medicine Valley Medical Center	Renton	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Janssen Research & Development, LLC

Countries where clinical trial is conducted

United States,  France,  Korea, Republic of,  Spain,  Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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)
Secondary	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)
Secondary	Percentage of Participants with IRRs	Percentage of participants with IRRs will be reported.	Up to 30 days after end of treatment (14 months)
Secondary	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)
Secondary	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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