Premedication to Mitigate Amivantamab Infusion Related Reactions

Sponsor

Janssen Research & Development, LLC (Industry)

Overall Status

Not yet recruiting

CT.gov ID

NCT05663866

Collaborator

(none)

120

Enrollment

Locations

Arm

14.7

Anticipated Duration (Months)

6.7

Patients Per Site

0.5

Patients Per Site Per Month

Study Details

Study Description

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 infusion related reaction (IRR), when amivantamab is given in combination with Lazertinib (by mouth), to reduce first-dose IRRs.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Dexamethasone Drug: Montelukast Drug: Methotrexate Drug: Amivantamab Drug: Lazertinib	Phase 2

Detailed Description

Amivantamab is a bispecific epidermal growth factor receptor (EGF) receptor-directed and mesenchymal epithelial transition (MET) receptor-directed antibody with immune cell directing activity, which has received accelerated approval for the treatment of adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 20 insertion mutations, after progression on or after platinum-based chemotherapy. Amivantamab given IV can cause IRRs. Lazertinib is a third-generation EGFR tyrosine kinase inhibitor (TKI) approved in the Republic of Korea for the treatment of patients with locally advanced or metastatic EGFR T790M mutation-positive NSCLC who have progressed on or after EGFR TKI therapy. The study consists of a screening period (up to 25 days), prophylaxis administration period (5 days), a treatment Phase (from cycle 1 Day 1 until the end of treatment visit) and end of study (up to 30 days after last dose). The safety of the study treatments (dexamethasone, montelukast, and methotrexate) and of the background anti-cancer therapy (intravenous [IV] amivantamab and lazertinib) will be assessed by physical examinations, clinical laboratory tests, vital signs, monitoring of adverse events (AEs), and concomitant medication usage. The total duration of the study is up to 14 months.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of Amivantamab Infusion Related Reaction Mitigation

Anticipated Study Start Date :

Apr 9, 2023

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Background Anti-cancer Therapy with Amivantamab Plus Lazertinib Participant will receive following treatments in 3 different cohorts prior to administration of combination therapy of IV Amivantamab and oral Lazertinib (anti-cancer regimen): dexamethasone in Cohort A; montelukast in Cohort B; and methotrexate in Cohort C.	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 Names: JNJ-61186372 Drug: Lazertinib Lazertinib tablets will be administered orally. Other Names: JNJ-73841937

Arm

Intervention/Treatment

Experimental: Background Anti-cancer Therapy with Amivantamab Plus Lazertinib

Participant will receive following treatments in 3 different cohorts prior to administration of combination therapy of IV Amivantamab and oral Lazertinib (anti-cancer regimen): dexamethasone in Cohort A; montelukast in Cohort B; and methotrexate in Cohort C.

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 Names:

JNJ-61186372

Drug: Lazertinib

Lazertinib tablets will be administered orally.

Other Names:

JNJ-73841937

Outcome Measures

Primary Outcome Measures

Percentage of Participants with Infusion-related Reactions (IRRs) [Cycle 1 Day 1]
Percentage of participants with IRRs will be reported.

Secondary Outcome Measures

Percentage of Participants with Adverse Events (AEs) of Infusion-related Reactions (IRRs) at Cycle 1 Day 1 [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 [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 [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 [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 [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 [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) [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 [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 [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) [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) [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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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, lazertinib and intravenous (IV) Amivantamab
Each participant 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

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 contraindications, allergies, hypersensitivity, or intolerance to lazertinib, IV amivantamab, dexamethasone, montelukast, methotrexate or their excipients. Methotrexate is contraindicated in pregnancy, alcoholism or liver disease, immunodeficiency syndromes, preexisting blood dyscrasias, and hypersensitivity to methotrexate

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Compassionate Cancer Care	Fountain Valley	California	United States	92708
2	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031
3	CHU Brest	Brest		France	29200
4	Hopital Europeen Georges-Pompidou	Paris		France	75015
5	CHU Rouen - Hopital Charles Nicolle	Rouen Cedex		France	76000
6	Nouvel Hopital Civil - CHU Strasbourg	Strasbourg CEDEX		France	67091
7	National Cancer Center	Gyeonggi-do		Korea, Republic of	10408
8	Seoul National University Bundang Hospital	Gyeonggi-do		Korea, Republic of	13620
9	Gachon University Gil Medical Center	Incheon		Korea, Republic of	21565
10	Chonnam National University Hwasun Hospital	Jeollanam-do		Korea, Republic of	58128
11	Hosp. de la Santa Creu i Sant Pau	Barcelona		Spain	08025
12	Inst. Cat. Doncologia-H Duran I Reynals	L'Hospitalet de Llobregat		Spain	08908
13	Md Anderson Cancer Center Madrid	Madrid		Spain	28033
14	Hosp. Univ. 12 de Octubre	Madrid		Spain	28041
15	Hosp. Virgen de La Victoria	Málaga		Spain	29010
16	Hosp. Clinico Univ. de Santiago	Santiago de Compostela		Spain	15706
17	Hosp. Gral. Univ. Valencia	Valencia		Spain	46014
18	Hosp. Clinico Univ. Lozano Blesa	Zaragoza		Spain	50009