RYBREVANT®▼ (amivantamab) plus chemotherapy show 49 percent overall response rate in metastatic colorectal cancer

Median duration of response reaches 7.4 months with combination treatment in patients with aggressive form of disease¹

New results show potential of amivantamab beyond lung cancer¹

BEERSE, BELGIUM, Sept. 14, 2024 (GLOBE NEWSWIRE) — Janssen-Cilag International NV, a Johnson & Johnson company, today announced new data from the Phase 1b/2 OrigAMI-1 study, which showed amivantamab combined with chemotherapy (mFOLFOX6 [FOLFOX] or FOLFIRI) demonstrated promising rapid and durable antitumour activity in patients with RAS/BRAF wild-type (WT) metastatic colorectal cancer (mCRC) who have not previously received anti-epidermal growth factor receptor (EGFR) therapy.¹ These data were presented in a mini-oral presentation at the European Society of Medical Oncology (ESMO) 2024 Congress, taking place in Barcelona, Spain from 13-17 September.¹

“OrigAMI-1 is the first study to show amivantamab plus chemotherapy may provide clinically meaningful benefits to patients with metastatic colorectal cancer who have not received any EGFR-targeted treatments as their first or second line of therapy,” said Filippo Pietrantonio, M.D., Medical Oncologist at Fondazione IRCCS Istituto Nazionale dei Tumori in Milan, Italy, and presenting author.* “Notably, we saw 21 percent of patients proceed to curative intent surgery, showing the promise of amivantamab in patients in this setting.”

In the study, patients receiving amivantamab plus chemotherapy were either in their first (26 percent) or second line (74 percent) of treatment for mCRC and had not been treated with specific anti-EGFR therapies.¹ Patients receiving FOLFOX were oxaliplatin-naïve and patients receiving FOLFIRI were irinotecan-naïve.² Response was assessed by the investigator per RECIST v1.1.^{2 †} Forty-three patients were treated with amivantamab along with either FOLFOX (20 patients) or FOLFIRI (23 patients).¹ The median follow-up period was 7.3 months for amivantamab plus FOLFOX and amivantamab plus FOLFIRI.¹

Patients treated with amivantamab plus chemotherapy achieved an overall response rate (ORR) of 49 percent (95 percent confidence interval [CI], 33-65), median duration of response of 7.4 months (95 percent CI, 5.6-not estimable [NE]) and median progression-free survival of 7.5 months (95 percent CI, 7.4‒NE).¹ Disease control was observed in 88 percent of patients (95 percent CI, 75-96).¹ Clinically meaningful intrahepatic antitumour activity was observed among patients with liver metastases treated with amivantamab plus chemotherapy, demonstrating a significant reduction in liver tumours (ORR of 53 percent, disease control rate of 93 percent).¹ Notably, nine (21 percent) patients were able to proceed to curative intent surgery due to strong antitumour activity.¹  

“About 20 percent of patients have metastatic colorectal cancer when they are diagnosed and another 40 percent have recurrence of their cancer with metastases after initial treatment, making the need for new, targeted treatment options critical,” said Henar Hevia, Ph.D., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “The latest results from the OrigAMI-1 study demonstrate the potential of this amivantamab-based combination regimen, with its multi-targeted mechanism of action, to address an important unmet need in metastatic colorectal cancer.”

The safety profile of amivantamab plus FOLFOX/FOLFIRI was manageable and consistent with each of the individual components, without any additive toxicity.¹ No new safety signals were observed.¹ The most frequent treatment-emergent adverse events were neutropenia, rash, stomatitis, infusion-related reactions (IRRs) and diarrhoea.¹ All IRRs were Grade 1 or 2 and there were no Grade 3 or higher IRR events reported.¹ Treatment-related discontinuations of amivantamab were 10 percent for amivantamab plus FOLFOX and nine percent for amivantamab plus FOLFIRI.¹

“Confirmation that amivantamab has activity beyond lung cancer, given its unique multi-targeted approach in inhibiting EGFR and MET, is a potentially important step forward for patients with EGFR inhibitor-naïve metastatic colorectal cancer,” said Kiran Patel, M.D., Vice President, Clinical Development, Solid Tumors, Johnson & Johnson Innovative Medicine. “Colorectal cancer is the third most common cancer globally, representing about 10 percent of all cancer cases and the second leading cause of cancer-related deaths. Our commitment to advancing cancer care drives us to evaluate every possibility to improve patient outcomes, and these findings highlight the potential of amivantamab to help even more patients with cancer.”

Pivotal Phase 3 registration trials evaluating amivantamab-based regimens as first- and second-line treatment in colorectal cancer are planned. 

About the OrigAMI-1 Study
OrigAMI-1 (NCT05379595) is an open-label Phase 1b/2 study assessing the efficacy and safety of amivantamab plus mFOLFOX6 or FOLFIRI in anti-EGFR-naïve RAS/BRAF WT mCRC.² Eligible patients were WT for  KRAS, NRAS and BRAF genes based on circulating tumour DNA testing.² Additionally, patients were required to have no amplification of the ERBB2/HER2 gene. In the amivantamab and chemotherapy cohorts, patients were either treatment-naïve or had received at least one prior line in the metastatic setting (no EGFR inhibitor treatment).² The primary endpoint of the combination cohorts was to characterise the safety and confirm the dose of amivantamab plus mFOLFOX6 or FOLFIRI.²  Response was assessed by the investigator per RECIST v1.1.^2†

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.^3,4,5,6

The European Commission (EC) has granted marketing authorisation of amivantamab in the following indications:⁷

• In combination with carboplatin and pemetrexed, for the first-line treatment of adult patients with advanced non-small cell lung cancer (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 (ex19del) or L858R substitution mutations, after failure of prior therapy including an EGFR 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.⁸ 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.⁹

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.⁷

▼ In line with EMA regulations for new medicines, amivantamab is subject to additional monitoring.   

About Colorectal Cancer
Colorectal cancer is the third most common cancer worldwide and the second most common cancer in Europe, with over 538,000 people diagnosed in 2022.^10,11 While it predominantly affects older individuals, recent research suggests that colorectal cancer is now being diagnosed in adults under the age of 50 at record rates.¹²

Left-sided colorectal cancer, which represents approximately 65 percent of cases, often has distinct characteristics that influence treatment strategies.¹³ Around half of colorectal cancer patients have mutations in the RAS genes, with KRAS being the most common mutation.^14,15 While tumours with normal RAS and BRAF genes generally respond better to EGFR inhibitors, those with RAS and BRAF mutations are associated with poorer outcomes.^14,16,17,18

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 www.linkedin.com/company/jnj-innovative-medicine-emea. Janssen Research & Development, LLC, 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. 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-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-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. Filippo Pietrantonio has provided consulting, advisory, and speaking services to Johnson & Johnson; he has not been paid for any media work. 

^†RECIST (version 1.1) refers to Response Evaluation Criteria in Solid Tumors, which is a standard way to measure how well solid tumours respond to treatment and is based on whether tumours shrink, stay the same or get bigger.

¹ Pietrantonio, et al. Amivantamab plus FOLFOX or FOLFIRI in metastatic colorectal cancer: Results from OrigAMI-1, a phase 1b/2 study. 2024 European Society for Medical Oncology. September 14, 2024.

² ClinicalTrials.gov. A Study of Amivantamab Monotherapy and in Addition to Standard-of-Care Chemotherapy in Participants With Advanced or Metastatic Colorectal Cancer (OrigAMI-1). https://clinicaltrials.gov/study/NCT05379595?tab=history&a=1. Accessed September 2024.

³ 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.

⁴ 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.

⁵ 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.

⁶ 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.

⁷ European Medicines Agency. Amivantamab Summary of Product Characteristics. August 2024. Available at https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf. Accessed September 2024.

⁸ 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. Available at: https://www.janssen.com/emea/sites/www_janssen_com_emea/files/amivantamab_mariposa_ema_filing_release_2024_2.pdf. Accessed: September 2024.

⁹ Janssen 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.

¹⁰ World Health Organization. Colorectal Cancer. 2022. Available at: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer. Accessed: September 2024

¹¹ Globocan. Europe Cancer Factsheet 2022. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/908-europe-fact-sheet.pdf. Accessed: September 2024.

¹² Virostko J, et al. Recent trends in the age at diagnosis of colorectal cancer in the US National Cancer Data Base, 2004-2015. Cancer, 2019;125: 3828-3835. https://doi.org/10.1002/cncr.32347.

¹³ Bellio H, et al. Targeting BRAF and RAS in Colorectal Cancer. Cancers (Basel). 2021 May 3;13(9):2201. doi: 10.3390/cancers13092201.

¹⁴ Janssen JBE, et al. Mutant RAS and the tumor microenvironment as dual therapeutic targets for advanced colorectal cancer. Cancer Treat Rev. 2022 Sep;109:102433. 

¹⁵ Dinu D, et al. Prognostic significance of KRAS gene mutations in colorectal cancer–preliminary study. J Med Life. 2014 Oct
Dec;7(4):581-7. 

¹⁶ Christopher H. Lieu et al., Integrating Biomarkers and Targeted Therapy Into Colorectal Cancer Management. Am Soc Clin Oncol Educ Book 39, 207-215(2019). DOI:10.1200/EDBK_240839.

¹⁷ Clarke CN, et al. RAF mutant colorectal cancer as a distinct subset of colorectal cancer: clinical characteristics, clinical behavior, and response to targeted therapies. J Gastrointest Oncol. 2015 Dec;6(6):660-7. 

¹⁸ Randon G, et al. Negative Ultraselection of Patients With RAS/BRAF Wild-Type, Microsatellite-Stable Metastatic Colorectal Cancer Receiving Anti-EGFR-Based Therapy. JCO Precis Oncol. 2022 Apr;6:e2200037.

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