Premedication to Reduce Amivantamab Associated Infusion Related Reactions

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

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Lazertinib; Drug: Dexamethasone; Drug: Amivantamab; Drug: Montelukast; Drug: Methotrexate

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 Type: Interventional
• Enrollment (Actual): 68
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Brest, France, 29200
    • CHU de Brest - Hôpital de la Cavale Blanche
  • Lyon, France, 69008
    • Centre Leon Berard
  • Paris, France, 75015
    • Hôpital européen Georges-Pompidou
  • Paris, France, 75014
    • Hôpital Cochin
  • Rouen, France, 76000
    • CHU Rouen Hopital Charles Nicolle
  • Strasbourg, France, 67091
    • Nouvel Hopital Civil - CHU Strasbourg
• South Korea
  • Cheongju-si, South Korea, 28644
    • Chungbuk National University Hospital
  • Gyeonggi-do, South Korea, 10408
    • National Cancer Center
  • Incheon, South Korea, 21565
    • Gachon University Gil Medical Center
  • Jeollanam-do, South Korea, 58128
    • Chonnam National University Hwasun Hospital
  • Seongnam-si, South Korea, 13620
    • Seoul National University Bundang Hospital
  • Seoul, South Korea, 05505
    • Asan Medical Center
• Spain
  • Barcelona, Spain, 08025
    • Hosp. de La Santa Creu I Sant Pau
  • Barcelona, Spain, 8028
    • Hosp. Univ. Quiron Dexeus
  • Barcelona, Spain, 08035
    • Hosp Univ Vall D Hebron
  • Cáceres, Spain, 10003
    • Hosp. San Pedro de Alcantara
  • Jerez de la Frontera, Spain, 11407
    • Hosp. de Jerez de La Frontera
  • L'Hospitalet de Llobregat, Spain, 08908
    • Inst. Cat. Doncologia-H Duran I Reynals
  • Madrid, Spain, 28041
    • Hosp. Univ. 12 de Octubre
  • Madrid, Spain, 28007
    • Hosp. Gral. Univ. Gregorio Maranon
  • Málaga, Spain, 29010
    • Hosp Virgen de La Victoria
  • Palma de Mallorca, Spain, 07120
    • Hosp. Univ. Son Espases
  • Santiago de Compostela, Spain, 15706
    • Hosp. Clinico Univ. de Santiago
  • Valencia, Spain, 46014
    • Hosp. Gral. Univ. Valencia
  • Valencia, Spain, 46009
    • Inst. Valenciano de Oncologia
  • Zaragoza, Spain, 50009
    • Hosp. Clinico Univ. Lozano Blesa
• Taiwan
  • Changhua, Taiwan, 500
    • Changhua Christian Hospital
  • Kaohsiung City, Taiwan, 80756
    • Kaohsiung Medical University Chung Ho Memorial Hospital
  • Taichung, Taiwan, 40705
    • Taichung Veterans General Hospital
  • Tainan, Taiwan, 73657
    • Chi-Mei Medical Center, Liouying
  • Taipei, Taiwan, 110
    • Taipei Medical University
  • Taipei, Taiwan, 112
    • Taipei Veterans General Hospital
  • Taipei, Taiwan, 10043
    • National Taiwan University Hospital
• United States
  • California
    • Fountain Valley, California, United States, 92708
      • Compassionate Cancer Care
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists
  • Washington
    • Renton, Washington, United States, 98055
      • UW Medicine Valley Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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.	Drug: Lazertinib; Lazertinib tablets will be administered orally.; Other Names: JNJ-73841937; Drug: Dexamethasone; Dexamethasone will be administered orally.; Drug: Amivantamab; Amivantamab will be administered intravenously.; Other Names: JNJ-61186372; Drug: Montelukast; Montelukast will be administered orally.; Drug: Methotrexate; Methotrexate will be administered subcutaneously.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Infusion-related Reactions (IRRs) at Cycle 1 Day 1	Percentage of participants with IRRs at Cycle 1 Day 1 was reported. IRRs were defined as IRR 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. IRR included chills, dyspnea, flushing, nausea, chest discomfort, vomiting, tachycardia, hypotension, and fever. IRRs that occurred on Cycle 1 Day 2 pre-infusion were considered under Cycle 1 Day 1.	Cycle 1 Day 1 (each cycle of 28 days)

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of Participants With Adverse Events of Infusion-related Reactions (IRRs) During Cycle 1 Day 1	Cycle 1 Day 1 (each cycle of 28 days)
Percentage of Participants With Adverse Events (AEs) of Infusion-related Reactions (IRRs) as Per Severity up to End of Cycle 3 (Cycle 3 Day 28)	From Cycle 1 Day 1 up to Cycle 3 Day 28 (each cycle of 28 days)
Percentage of Participants With IRRs up to End of Treatment (EOT)	From Cycle 1 Day 1 (each cycle of 28 days) up to 27.3 months
Percentage of Participants With Other Adverse Events (AEs): Non-IRRs	From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months
Duration of Infusion Time for Pre-amivantamab Infusion Medications, IV Amivantamab Infusion, and Post-amivantamab Infusion Medications on Cycle 1 Day 1	Cycle 1 Day 1 (each cycle of 28 days)
Percentage of Participants Completing Amivantamab Infusion Within 4 Hours on Cycle 1 Day 1	Up to 4 hours on Cycle 1 Day 1 (each cycle of 28 days)
Overall Response Rate (ORR)	From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months
Duration of Response (DOR)	From Cycle 1 Day 1 (each cycle of 28 days) up to 28.3 months

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Spira AI, Paz-Ares L, Han JY, Shih JY, Mascaux C, Roy UB, Zugazagoitia J, Kim YJ, Chiu CH, Kim SW, Nadal E, Gil-Bazo I, Murphy SP, Anderson BG, Xia Y, Wang G, Bauml JM, Chioda M, Simoes J, Mahadevia PJ, Lopes G. Preventing Infusion-Related Reactions With Intravenous Amivantamab-Results From SKIPPirr, a Phase 2 Study: A Brief Report. J Thorac Oncol. 2025 Jun;20(6):809-816. doi: 10.1016/j.jtho.2025.01.018. Epub 2025 Jan 24.

Study record dates

Study Major Dates

• Study Start (Actual): May 18, 2023
• Primary Completion (Actual): March 29, 2024
• Study Completion (Estimated): March 31, 2027

Study Registration Dates

• First Submitted: December 16, 2022
• First Submitted That Met QC Criteria: December 16, 2022
• First Posted (Actual): December 23, 2022

Study Record Updates

• Last Update Posted (Actual): June 8, 2026
• Last Update Submitted That Met QC Criteria: June 4, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Respiratory Tract Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Carcinoma, Non-Small-Cell Lung; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Polycyclic Compounds; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Steroids, Fluorinated; Pterins; Pteridines; Pregnadienetriols; Aminopterin; Dexamethasone; Methotrexate; amivantamab; lazertinib; montelukast
• 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)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD 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

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No