The 8 mg pre-medication regimen showed an infusion-related reaction rate of 22.5 percent with intravenous amivantamab, a three-fold reduction from 67.4 percent historically seen with standard IRR management1,2
BEERSE, BELGIUM, Sept. 10, 2024 (GLOBE NEWSWIRE) -- Janssen-Cilag International NV, a Johnson & Johnson company, today announced results from the open-label Phase 2 SKIPPirr study, which evaluated additional prophylactic strategies to reduce the incidence of infusion-related reactions (IRRs) with intravenous (IV) RYBREVANT®▼ (amivantamab) in patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or L858R substitution mutations.1 Many monoclonal antibodies are associated with increased rates of IRRs and IRRs with amivantamab are of special interest to the European Medicines Agency (EMA).2,3 The study, which included 40 patients, showed that prophylaxis with 8 mg dexamethasone taken for two days prior to the first infusion met the primary endpoint of incidence of IRRs at Cycle 1 Day 1 (C1D1), with an all-grades IRR rate for IV amivantamab of 22.5 percent.1 There were three additional arms to the study exploring different prophylactic regimens: group 1 (dexamethasone 4 mg, one dose taken orally twice daily on the day before treatment ), group 3 (montelukast 10 mg, five doses starting four days before treatment and continuing through the day of treatment) and group 4 (methotrexate 25 mg subcutaneous injection, administered between days 7 and 3 before treatment).1 Group 1, 3 and 4 were stopped for futility.1 The results of group 2 (dexamethasone 8 mg, taken for two days prior to infusion) showed a three-fold reduction in the incidence of IRRs compared to standard management of IRRs with IV amivantamab, where historic data has observed an all-grades incidence rate of 67.4 percent.1,2 Data were presented as a mini-oral presentation at the International Association for the Study of Lung Cancer (IASLC) 2024 World Conference on Lung Cancer (WCLC) taking place in San Diego, California from 7-10 September (Abstract #1785).1
“These data offer important insights that may help improve the patient experience with intravenous amivantamab treatment,” said Gilberto Lopes, M.D., Associate Director of Global Oncology at Sylvester Comprehensive Cancer Center, part of the University of Miami Miller School of Medicine, and presenting author.* “This study shows us that an easily accessible approach of an increased dose regimen of dexamethasone as a pre-treatment prophylaxis can potentially help lower IRRs. It is encouraging to see a three-fold decrease in IRRs, when comparing the rates in SKIPPirr to historical data.”
“At Johnson & Johnson, we are deeply committed to advancing patient care and improving the treatment experience for those with EGFR-mutated non-small cell lung cancer,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The findings of this study show the value of comprehensive management strategies, including prophylactic interventions like dexamethasone, in reducing IRRs and optimising treatment experience with intravenous amivantamab and oral lazertinib.”
In the study, patients received an at-home regimen of oral dexamethasone, taking an 8 mg dose twice daily on the two prior days and one dose one hour prior to receiving IV amivantamab, in addition to the standard prophylactic regimen.1 The amivantamab treatment was combined with lazertinib.1 All IRRs were Grade 1 or 2 with no patients requiring hospitalisation due to IRRs.1 There were no Grade 3 or higher IRR events reported.1 The safety profile of amivantamab and lazertinib with prophylactic dexamethasone at the initiation of treatment was otherwise consistent with previous studies.1 The most common IRR-related symptoms observed in the study were nausea (8 percent), dyspnea (5 percent) and hypotension (5 percent).1
“Reducing the risk of IRRs is a critical aspect of improving the overall treatment experience for patients receiving intravenous amivantamab and oral lazertinib,” said Mark Wildgust, Ph.D., Vice President of Oncology Global Medical Affairs, Johnson & Johnson Innovative Medicine. “By incorporating an additional treatment regimen of prophylactic oral dexamethasone we can help mitigate this risk, with the goal of allowing patients to continue their therapy with fewer interruptions.”
Additional studies are ongoing to evaluate prophylactic strategies to reduce IRRs for patients receiving IV amivantamab.
About the SKIPPirr Study
SKIPPirr (NCT05663866) is a Phase 2 study evaluating amivantamab in combination with lazertinib in patients with EGFR-mutated (Ex19del or L858R) advanced NSCLC after disease progression on osimertinib and platinum-based chemotherapy.1,4 All patients received oral lazertinib and IV amivantamab.1 The study used a Simon’s 2-stage design to evaluate different preventive treatments across four groups.1 The first group received dexamethasone (4 mg) orally, taken twice daily on the day before treatment, for a total of two doses.1 The second group was given a higher dose of dexamethasone (8 mg), taken orally twice daily on the two days leading up to treatment and the morning of infusion (5 doses total).1 The third group received montelukast (10 mg) orally, starting four days before treatment and continuing through the day of treatment, totaling five doses.1 Lastly, the fourth group was treated with a single dose of methotrexate (25 mg), administered as a subcutaneous injection between days 7 and 3 before the treatment.1 The primary endpoint of the study is incidence of IRRs at Cycle 1 Day 1.1
About Amivantamab
Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system.5,6,7,8
The European Commission (EC) has granted marketing authorisation of amivantamab in the following indications:9
- In combination with carboplatin and pemetrexed, for the first-line treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations
- As monotherapy, for treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations, after failure of platinum-based therapy
- In combination with carboplatin and pemetrexed, for the treatment of adult patients with advanced NSCLC with EGFR exon 19 deletions or L858R substitution mutations, after failure of prior therapy including an EGFR tyrosine kinase inhibitor (TKI)
In February 2024, a Type II extension of indication application was submitted to the EMA based on the MARIPOSA study, for amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with common EGFR ex19del or L858R substitution mutations.10 In May 2024, an application for the extension of the amivantamab marketing authorisation was submitted seeking approval for the use of a subcutaneous (SC) formulation of amivantamab in combination with lazertinib for the first-line treatment of adult patients with advanced NSCLC with EGFR ex19del or L858R mutations, and for the use of SC amivantamab monotherapy in adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy.11
For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using amivantamab, please refer to the Summary of Product Characteristics.9
▼ In line with EMA regulations for new medicines, amivantamab is subject to additional monitoring.
About Non-Small Cell Lung Cancer
In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022.12 NSCLC accounts for 85 percent of all lung cancer cases.13 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined.12
The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma.13 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division.13,14 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients.15,16,17,18 EGFR ex19del or EGFR L858R mutations are the most common EGFR mutations.19 The five-year survival rate for all people with advanced NSCLC and EGFR mutations treated with EGFR tyrosine kinase inhibitors (TKIs) is less than 20 percent and between 25-32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment.20,21,22
About Johnson & Johnson
At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow, and profoundly impact health for humanity.
Learn more at www.janssen.com/emea. Follow us at http://www.linkedin.com/company/jnj-innovative-medicine-emea/. Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and Janssen-Cilag International NV are Johnson & Johnson companies.
Cautions Concerning Forward-Looking Statements
This press release contains “forward-looking statements” as defined in the Private Securities Litigation Reform Act of 1995 regarding product development and the potential benefits and treatment impact of amivantamab and lazertinib. The reader is cautioned not to rely on these forward-looking statements. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or known or unknown risks or uncertainties materialise, actual results could vary materially from the expectations and projections of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and Janssen-Cilag International NV, and/or Johnson & Johnson. Risks and uncertainties include, but are not limited to: challenges and uncertainties inherent in product research and development, including the uncertainty of clinical success and of obtaining regulatory approvals; uncertainty of commercial success; manufacturing difficulties and delays; competition, including technological advances, new products and patents attained by competitors; challenges to patents; product efficacy or safety concerns resulting in product recalls or regulatory action; changes in behaviour and spending patterns of purchasers of health care products and services; changes to applicable laws and regulations, including global health care reforms; and trends toward health care cost containment. A further list and descriptions of these risks, uncertainties and other factors can be found in Johnson & Johnson’s Annual Report on Form 10-K for the fiscal year ended December 31, 2023, including in the sections captioned “Cautionary Note Regarding Forward-Looking Statements” and “Item 1A. Risk Factors,” and in Johnson & Johnson’s subsequent Quarterly Reports on Form 10-Q and other filings with the Securities and Exchange Commission. Copies of these filings are available online at http://www.sec.gov/, http://www.jnj.com/ or on request from Johnson & Johnson. None of Janssen Research & Development, LLC, Janssen Biotech, Inc., Janssen-Cilag, S.A. and Janssen-Cilag International NV, nor Johnson & Johnson undertakes to update any forward-looking statement as a result of new information or future events or developments.
© Janssen-Cilag International NV, Inc. 2024. All rights reserved.
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*Dr. Gilberto Lopes has served as a consultant to Janssen-Cilag International NV; he has not been paid for any media work.
References:
1 Lopes G, et al. Preventing Infusion-related Reactions with Intravenous Amivantamab: Primary Results From SKIPPirr, a Phase 2 Study. Oral Presentation, IASLC WCLC 2024. September 10, 2024.
2 Park K, Sabari JK, Haura EB, et al. Management of infusion-related reactions (IRRs) in patients receiving amivantamab in the CHRYSALIS study. Lung Cancer. 2023;178:166-171.
3 Barroso A, et al. Management of infusion-related reactions in cancer therapy: strategies and challenges. ESMO Open. 2024;9(3):102922.
4 ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). Available at: https://clinicaltrials.gov/study/NCT05663866 Accessed: September 2024.
5 Grugan KD, et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. MAbs 2017;9(1):114-126.
6 Moores SL, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res 2016;76(13)(suppl 27216193):3942-3953.
7 Yun J, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion–Driven NSCLC. Cancer Discov 2020;10(8):1194-1209.
8 Vijayaraghavan S, et al. Amivantamab (JNJ-61186372), an Fc Enhanced EGFR/cMet Bispecific Antibody, Induces Receptor Downmodulation and Antitumor Activity by Monocyte/Macrophage Trogocytosis. Mol Cancer Ther 2020;19(10):2044-2056.
9 European Medicines Agency. Amivantamab Summary of Product Characteristics. July 2024. Available at: https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf Accessed: September 2024.
10 Janssen.com/EMEA. Janssen Submits Type II Extension of Indication Application to the European Medicines Agency Seeking Approval of RYBREVANT®▼ (amivantamab), in combination with Lazertinib, for the First-Line Treatment of Patients with EGFR Mutated Non-Small Cell Lung Cancer. https://www.janssen.com/emea/sites/www_janssen_com_emea/files/amivantamab_mariposa_ema_filing_release_2024_2.pdf. Accessed: September 2024.
11 Janssen.com/EMEA. Johnson & Johnson submits application to the European Medicines Agency seeking approval of subcutaneous formulation of RYBREVANT®▼ (amivantamab) for the treatment of patients with EGFR-mutated non-small cell lung cancer. Available at: https://www.janssen.com/sites/www_janssen_com_emea/files/jj_asco_paloma-3_-_ema_filing_press_release.pdf Accessed: September 2024.
12 Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf. Accessed: September 2024.
13 Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res 2016;5(3):288–300.
14 Wee P & Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers 2017;9(12):52.
15 Pennell NA, et al. A phase II trial of adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol 2019;37(2):97-104.
16 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting (Singapore); January 29, 2021.
17 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget. 2016;7(48):78985-78993.
18 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res 2015;5(9):2892-2911.
19 American Lung Association. EGFR and Lung Cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr. Accessed: September 2024.
20 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol 2016 Apr;11(4):556-65.
21 Nieva J, et al. A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC). Ann Oncol 2023;34, S774.
22 Girard N, et al. Mortality among EGFR-mutated advanced NSCLC patients after frontline osimertinib treatment: A real-world, US attrition analysis. J Thorac Oncol 2023;18(4), S51-52.
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