RYBREVANT® (amivantamab-vmjw) 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 disease

New results show potential of RYBREVANT^® beyond lung cancer

BARCELONA, Spain I September 14, 2024 I Johnson & Johnson (NYSE:JNJ) today announced new data from the Phase 1b/2 OrigAMI-1 study, which showed RYBREVANT^® (amivantamab-vmjw) combined with chemotherapy (mFOLFOX6 [FOLFOX] or FOLFIRI) demonstrated promising rapid and durable antitumor 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. These data were presented in a mini-oral presentation at the European Society of Medical Oncology (ESMO) 2024 Congress.¹

“OrigAMI-1 is the first study to show RYBREVANT 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 RYBREVANT in patients in this setting.”

In the study, patients receiving RYBREVANT^® 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. Patients receiving FOLFOX were oxaliplatin-naïve and patients receiving FOLFIRI were irinotecan-naïve. Response was assessed by the investigator per RECIST v1.1.** Forty-three patients were treated with RYBREVANT^® along with either FOLFOX (20 patients) or FOLFIRI (23 patients). The median follow-up period was 7.3 months for RYBREVANT^® plus FOLFOX and RYBREVANT^® plus FOLFIRI.¹

Patients treated with RYBREVANT^® 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). Disease control was observed in 88 percent of patients (95 percent CI, 75-96). Clinically meaningful intrahepatic antitumor activity was observed among patients with liver metastases treated with RYBREVANT^® plus chemotherapy, demonstrating a significant reduction in liver tumors (ORR of 53 percent, disease control rate of 93 percent). Notably, nine (21 percent) patients were able to proceed to curative-intent surgery due to strong antitumor activity.¹

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

“Confirmation that RYBREVANT 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 RYBREVANT to help even more patients with cancer.”

Pivotal Phase 3 registration trials evaluating RYBREVANT^®-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 RYBREVANT^® plus mFOLFOX6 or FOLFIRI in anti-EGFR-naïve RAS/BRAF WT mCRC. Eligible patients were WT for KRAS, NRAS or BRAF genes based on circulating tumor DNA testing. Additionally, patients were required to have no amplification of the ERBB2/HER2 gene. In the RYBREVANT^® and chemotherapy cohorts, patients were either treatment-naïve or had received at least one prior line in the metastatic setting (no EGFR inhibitor treatment). The primary endpoint of the combination cohorts was to characterize the safety and confirm the dose of RYBREVANT^® plus mFOLFOX6 or FOLFIRI. Response was assessed by the investigator per RECIST v1.1.²

About RYBREVANT^®

RYBREVANT^® (amivantamab-vmjw), a fully-human bispecific antibody targeting EGFR and MET with immune cell-directing activity, is approved in the U.S., Europe, and in other markets around the world as monotherapy for the treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test, whose disease has progressed on or after platinum-based chemotherapy.³

RYBREVANT^® is approved in the U.S., Europe, and in markets around the world in combination with chemotherapy (carboplatin and pemetrexed) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 20 insertion mutations, as detected by an FDA-approved test. 

RYBREVANT^® is approved in the U.S. in combination with LAZCLUZE™ (lazertinib) for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or L858R substitution mutations, as detected by an FDA-approved test. A marketing authorization application (MAA) and type II extension of indication application were submitted to the European Medicines Agency (EMA) seeking approval of LAZCLUZE™ in combination with RYBREVANT^® based on the MARIPOSA study.

In November 2023, Johnson & Johnson submitted a supplemental Biologics License Application (sBLA) to the U.S. FDA for RYBREVANT^® in combination with chemotherapy for the treatment of patients with EGFR-mutated NSCLC who progressed on or after osimertinib based on the MARIPOSA-2 study. This indication was approved in Europe in August 2024.

In June 2024, Johnson & Johnson submitted a BLA to the U.S. FDA for the subcutaneous formulation of RYBREVANT^® in combination with LAZCLUZE™ for all currently approved or submitted indications of intravenous (IV) RYBREVANT^® in certain patients with NSCLC. A submission for the extension of the RYBREVANT^® marketing authorization (line extension) was also submitted to the EMA seeking approval for this indication. 

The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®) for NSCLC^§ prefer next-generation sequencing–based strategies over polymerase chain reaction–based approaches for the detection of EGFR exon 20 insertion variants. The NCCN Guidelines include:

• Amivantamab-vmjw (RYBREVANT^®) plus lazertinib (LAZCLUZE™) as a Category 1 recommendation for first-line therapy in patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations.^{4 †‡}
• Amivantamab-vmjw (RYBREVANT^®) plus chemotherapy as a Category 1 recommendation for patients with locally advanced or metastatic NCSLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib.^{4 †‡}
• Amivantamab-vmjw (RYBREVANT^®) plus carboplatin and pemetrexed as a Category 1 recommendation for first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion mutation-positive advanced NSCLC, or as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without immunotherapy and have EGFR exon 20 insertion mutation-positive advanced NSCLC.^{4 †‡}
• Amivantamab-vmjw (RYBREVANT^®) as a Category 2A recommendation for patients that have progressed on or after platinum-based chemotherapy with or without an immunotherapy and have EGFR exon 20 insertion mutation-positive NSCLC.^{4 †‡}

In addition to the Phase 1b/2 OrigAMI-1 study, RYBREVANT^® is being studied in multiple clinical trials, including:

• The Phase 3 MARIPOSA (NCT04487080) study assessing RYBREVANT^® in combination with LAZCLUZE™ versus osimertinib and versus LAZCLUZE™ alone in the first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or L858R substitution mutations.⁵
• The Phase 3 MARIPOSA-2 (NCT04988295) study assessing the efficacy of RYBREVANT^® (with or without LAZCLUZE™) carboplatin-pemetrexed versus carboplatin-pemetrexed alone in patients with locally advanced or metastatic EGFR ex19del or L858R substitution NSCLC after disease progression on or after osimertinib.⁶
• The Phase 3 PAPILLON (NCT04538664) study assessing RYBREVANT^® in combination with carboplatin-pemetrexed versus chemotherapy alone in the first-line treatment of patients with advanced or metastatic NSCLC with EGFR exon 20 insertion mutations.⁷
• The Phase 3 PALOMA-3 (NCT05388669) study assessing LAZCLUZE™ with subcutaneous amivantamab compared to intravenous amivantamab in patients with EGFR-mutated advanced or metastatic NSCLC.⁸
• The Phase 2 PALOMA-2 (NCT05498428) study assessing subcutaneous amivantamab in patients with advanced or metastatic solid tumors including EGFR-mutated NSCLC.⁹
• The Phase 1 PALOMA (NCT04606381) study assessing the feasibility of subcutaneous administration of amivantamab based on safety and pharmacokinetics and to determine a dose, dose regimen and formulation for amivantamab subcutaneous delivery.¹⁰
• The Phase 1 CHRYSALIS (NCT02609776) study evaluating RYBREVANT^® in patients with advanced NSCLC.¹¹
• The Phase 1/1b CHRYSALIS-2 (NCT04077463) study evaluating RYBREVANT^® in combination with LAZCLUZE™ and LAZCLUZE™ as a monotherapy in patients with advanced NSCLC with EGFR mutations.¹²
• The Phase 1/2 METalmark (NCT05488314) study assessing RYBREVANT^® and capmatinib combination therapy in locally advanced or metastatic NSCLC.¹³
• The Phase 1/2 PolyDamas (NCT05908734) study assessing RYBREVANT^® and cetrelimab combination therapy in locally advanced or metastatic NSCLC.¹⁴
• The Phase 2 SKIPPirr study (NCT05663866) exploring how to decrease the incidence and/or severity of first-dose infusion-related reactions with RYBREVANT^® in combination with LAZCLUZE™ in relapsed or refractory EGFR-mutated advanced or metastatic NSCLC.¹⁵
• The Phase 1/2 swalloWTail (NCT06532032) study assessing RYBREVANT^® and docetaxel combination therapy in patients with metastatic NSCLC.¹⁶
• The Phase 1b/2 OrigAMI-4 (NCT06385080) study assessing RYBREVANT^® monotherapy and in addition to standard-of-care therapeutic agents in patients with recurrent/metastatic head and neck squamous cell carcinoma.¹⁷

For more information, visit: https://www.RYBREVANT.com.

About Colorectal Cancer

Colorectal cancer is the third most common cancer worldwide, accounting for approximately 10 percent of all cancer cases and is the second leading cause of cancer-related deaths worldwide.¹⁸ 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.¹⁹

Left-sided colorectal cancer, which represents approximately 65 percent of cases, often has distinct characteristics that influence treatment strategies. Around half of colorectal cancer patients have mutations in the RAS genes, with KRAS being the most common mutation. While tumors with normal RAS and BRAF genes generally respond better to EGFR inhibitors, those with RAS and BRAF mutations – particularly on the left side – are associated with poorer outcomes.²⁰

Please read full Prescribing Information for RYBREVANT^®.

Please read full Prescribing Information for LAZCLUZE™.

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 https://www.jnj.com/ or at www.janssen.com/johnson-johnson-innovative-medicine. Follow us at @JanssenUS and @JNJInnovMed. Janssen Research & Development, LLC, and Janssen Biotech, Inc. are Johnson & Johnson companies. 

*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 tumors respond to treatment and is based on whether tumors shrink, stay the same or get bigger.

^†See the NCCN Guidelines for detailed recommendations, including other treatment options.

^‡The NCCN Guidelines for NSCLC provide recommendations for certain individual biomarkers that should be tested and recommend testing techniques but do not endorse any specific commercially available biomarker assays or commercial laboratories.

^§The NCCN Content does not constitute medical advice and should not be used in place of seeking professional medical advice, diagnosis or treatment by licensed practitioners. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.

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 RYBREVANT^® Prescribing Information. Horsham, PA: Janssen Biotech, Inc.
⁴ Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.9.2024© National Comprehensive Cancer Network, Inc. All rights reserved. To view the most recent and complete version of the guideline, go online to NCCN.org. Accessed September 2024.
⁵ ClinicalTrials.gov. A Study of Amivantamab and LAZCLUZE™ Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA). Available at: https://www.clinicaltrials.gov/study/NCT04487080. Accessed September 2024.
⁶ ClinicalTrials.gov. A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non-Small Cell Lung Cancer After Osimertinib Failure (MARIPOSA-2). Available at: https://classic.clinicaltrials.gov/ct2/show/study/NCT04988295. Accessed September 2024. 
⁷ ClinicalTrials.gov. A Study of Combination Amivantamab and Carboplatin-Pemetrexed Therapy, Compared With Carboplatin-Pemetrexed, in Participants With Advanced or Metastatic Non-Small Cell Lung Cancer Characterized by Epidermal Growth Factor Receptor (EGFR) Exon 20 Insertions (PAPILLON). Available at: https://clinicaltrials.gov/ct2/show/NCT04538664. Accessed September 2024.
⁸ ClinicalTrials.gov. A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669. Accessed September 2024.
⁹ ClinicalTrials.gov. A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (PALOMA-2). https://clinicaltrials.gov/ct2/show/NCT05498428. Accessed September 2024.
¹⁰ ClinicalTrials.gov. A Study of Amivantamab Subcutaneous (SC) Administration for the Treatment of Advanced Solid Malignancies (PALOMA). Available at: https://clinicaltrials.gov/study/NCT04606381. Accessed September 2024.
¹¹ ClinicalTrials.gov. A Study of Amivantamab, a Human Bispecific EGFR and cMet Antibody, in Participants With Advanced Non-Small Cell Lung Cancer (CHRYSALIS). https://clinicaltrials.gov/ct2/show/NCT02609776. Accessed September 2024.
¹² ClinicalTrials.gov. A Study of Lazertinib as Monotherapy or in Combination With Amivantamab in Participants With Advanced Non-small Cell Lung Cancer (CHRYSALIS-2). https://clinicaltrials.gov/ct2/show/NCT04077463. Accessed August 2024.
¹³ ClinicalTrials.gov. A Study of Amivantamab and Capmatinib Combination Therapy in Unresectable Metastatic Non-small Cell Lung Cancer (METalmark). https://clinicaltrials.gov/ct2/show/NCT05488314. Accessed September 2024.
¹⁴ ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Cetrelimab in Participants With Metastatic Non-small Cell Lung Cancer (PolyDamas). https://www.clinicaltrials.gov/study/NCT05908734?term=polydamas&rank=1. Accessed September 2024.
¹⁵ ClinicalTrials.gov. Premedication to Reduce Amivantamab Associated Infusion Related Reactions (SKIPPirr). https://classic.clinicaltrials.gov/ct2/show/NCT05663866. Accessed September 2024.
¹⁶ ClinicalTrials.gov. A Study of Combination Therapy With Amivantamab and Docetaxel in Participants With Metastatic Non-small Cell Lung Cancer (swalloWTail). https://www.clinicaltrials.gov/study/NCT06532032?term=Swallowtail&intr=amivantamab&rank=1. Accessed September 2024.
¹⁷ ClinicalTrials.gov. A Study of Amivantamab Alone or in Addition to Other Treatment Agents in Participants With Recurrent/ Metastatic Head and Neck Cancer (OrigAMI-4). https://clinicaltrials.gov/study/NCT06385080?term=OrigAMI-4&limit=10&rank=1. Accessed September 2024.
¹⁸ World Health Organization. Colorectal Cancer. 2022. Available at: https://www.who.int/news-room/fact-sheets/detail/colorectal-cancer. Accessed: July 2024
¹⁹ 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
²⁰ 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
²¹ LAZCLUZE™ Prescribing Information. Horsham, PA: Janssen Biotech, Inc.

SOURCE: Johnson & Johnson