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Responses were deep and durable, with 65% ongoing at clinical cutoff
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Results support continued evaluation of the investigational RYBREVANT FASPRO regimen in the ongoing first-line Phase 3 study
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Data highlight the role of dual-targeting EGFR and MET, key drivers of tumor growth and resistance seen in 80 to 90 percent of HNSCC
New Brunswick, N.J. October 25, 2026 /PR Newswire/ – Johnson & Johnson (NYSE:JNJ) today announced new results from Cohort 5 of the Phase 1b/2 OrigAMI-4 study showing deep and durable responses with first-line subcutaneous amivantamab and hyaluronidase-lpuj plus a PD-1 inhibitor and fixed-duration carboplatin chemotherapy in patients with recurrent or metastatic head and neck squamous cell carcinoma (HNSCC).1 These findings support the ongoing pivotal Phase 3 OrigAMI-5 study and further expand the clinical development program for subcutaneous amivantamab for patients with head and neck cancer.2
Among patients with HNSCC other than human papillomavirus (HPV)-associated oropharyngeal squamous cell carcinoma (OPSCC), results demonstrated a confirmed overall response rate (ORR) of 77 percent, including 14 percent achieving complete responses.1 Tumor shrinkage was observed in all evaluable patients, and nearly two-thirds of responses remained ongoing at a median follow-up of 10.6 months.1 These findings were presented as a rapid oral presentation at the European Society for Medical Oncology (ESMO) Congress 2026 (Abstract #1539RO). An application for RYBREVANT FASPRO in later-line head and neck cancer is also under Priority Review with the U.S. Food and Drug Administration (FDA).
Unmet need remains in first-line head and neck cancer treatment
For people with recurrent or metastatic head and neck cancer, the first treatment decision comes at a critical point in an aggressive disease often associated with poor prognosis.3 While some patients benefit from the current standard of care, many experience disease progression while facing symptoms that can profoundly affect daily life, including the ability to eat, swallow and speak.4,5 Nearly 60 percent of patients do not go on to receive subsequent treatment,6 underscoring the need to help more patients achieve meaningful tumor reduction and durable responses from the start.
Subcutaneous amivantamab is a bispecific antibody designed to dual-target epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition (MET) while also engaging the immune system.7,8,9 Overexpression of EGFR and MET is seen in 80 to 90 percent of HNSCC tumors and has been implicated in tumor progression and treatment resistance.10The approach has been well-validated in EGFR-mutated lung cancer where data suggest that targeting both pathways may disrupt disease biology and improve outcomes.11,12
Expert and company perspectives on RYBREVANT FASPRO’s role in advancing first-line treatment
“The first treatment a patient receives for recurrent or metastatic head and neck cancer can shape everything that follows,” said Paul Swiecicki, M.D.,* associate professor of Hematology/Oncology at University of Michigan Rogel Cancer Center. “The responses seen with subcutaneous amivantamab give us reason to think differently about what may be possible from the start of treatment, especially as we see responses across the majority of patients with head and neck cancer, excluding HPV-associated oropharyngeal squamous cell carcinoma, many of which are rapid, deep and persist over time.”
“We’ve already seen what subcutaneous amivantamab may offer patients with head and neck cancer after their disease has progressed. Now, we see the potential impact of using this approach earlier in recurrent or metastatic disease,” said Yusri Elsayed, M.D., M.H.Sc., Ph.D., Global Therapeutic Area Head, Oncology, Johnson & Johnson. “Our experience with RYBREVANT FASPRO in lung cancer has helped establish the potential of dual EGFR/MET targeting, and these results support continued evaluation of this approach in head and neck cancer.”
RYBREVANT FASPRO demonstrates meaningful anti-tumor activity in first-line disease
Cohort 5 of the OrigAMI-4 study evaluated subcutaneous amivantamab in combination with pembrolizumab (PD-1 inhibitor) and up to six cycles of carboplatin in previously untreated patients with recurrent or metastatic HNSCC. Patients received treatment every three weeks following the initial treatment period, with an administration time of five minutes or less. The primary endpoint was ORR, as assessed by investigators using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Response rates were assessed separately in patients with HPV-associated OPSCC (n=7) and patients with all other forms of HNSCC (n=22), given known differences in how these patient populations respond to EGFR-targeted bispecifics.1
Thirty patients received subcutaneous amivantamab in combination with pembrolizumab and carboplatin, and 29 were included in the efficacy analysis. One patient was deemed ineligible. Among the 22 patients with forms of HNSCC other than HPV-associated OPSCC, the confirmed ORR was 77 percent (95 percent confidence interval [CI], 55-92), including complete responses in 14 percent and partial responses in 64 percent. Responses occurred at a median of 9.4 weeks, with 65 percent ongoing at a median follow-up of 10.6 months. Four patients (18 percent) had stable disease and one (5 percent) had progressive disease. Median overall survival was not reached, and 77 percent of patients were alive at one year. The remaining seven patients had HPV-associated OPSCC, with an ORR of 29 percent (95 percent CI, 4-71).1
The safety profile of subcutaneous amivantamab in combination with pembrolizumab and carboplatin was consistent with the individual agents. The most common adverse events were anemia (73 percent), hypoalbuminemia (63 percent), thrombocytopenia (63 percent) and stomatitis (57 percent). Administration-related reactions associated with subcutaneous amivantamab occurred in 13 percent of patients, with no Grade 3 or higher events reported.1
The Cohort 5 findings build on earlier first-line results from the OrigAMI-4 program, including Cohort 2 data evaluating subcutaneous amivantamab in combination with pembrolizumab recently published in Clinical Cancer Research.13
About the OrigAMI-4 study
OrigAMI-4 (NCT06385080) is an open-label Phase 1b/2 study evaluating RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC). The study includes six cohorts exploring RYBREVANT FASPRO across different treatment settings and regimens.14
Cohort 5 of the OrigAMI-4 study evaluated RYBREVANT FASPRO, administered every three weeks, in combination with pembrolizumab and carboplatin in patients with recurrent or metastatic head and neck squamous cell carcinoma receiving first-line treatment whose tumors tested positive for programmed death-ligand 1 (PD-L1), with a combined positive score (CPS) of 1 or greater. The primary endpoint was ORR, as assessed by investigators using Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).† 14
About head and neck squamous cell carcinoma
Head and neck squamous cell carcinoma (HNSCC) is the most common form of head and neck cancer, a group of cancers that arise in the mouth, throat, voice box, sinuses, nasal cavity and salivary glands.15 It represents approximately 4.5 percent of all cancers worldwide and is the seventh most common cancer globally.15 Major risk factors include tobacco and alcohol use, as well as infection with high-risk human papillomavirus (HPV).15 Approximately 80 percent of recurrent or metastatic HNSCC are not driven by HPV, and are typically associated with poorer prognosis and reduced response to treatment.15,16 Despite advances in surgery, radiation, chemotherapy, and immunotherapy, many patients ultimately progress to advanced, recurrent or metastatic disease.17,18
About RYBREVANT FASPRO and RYBREVANT®
RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) received U.S. FDA approval in December 2025 and is approved in multiple markets worldwide for the treatment of adults with EGFR-mutated non-small cell lung cancer (NSCLC), including those with exon 19 deletions, exon 21 L858R substitution mutations, and exon 20 insertion mutations. It is the only subcutaneous therapy approved for these EGFR-mutated NSCLC populations and may be used as monotherapy or in combination with LAZCLUZE® (lazertinib) or chemotherapy, depending on the specific mutation and treatment setting. For eligible patients, RYBREVANT FASPRO offers a once-monthly dosing option following initial weekly dosing. RYBREVANT FASPRO is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE® drug delivery technology.
RYBREVANT FASPRO is approved in the U.S. for the same indications as intravenous RYBREVANT (amivantamab-vmjw) across multiple markets. RYBREVANT is a first-in-class, fully human bispecific antibody targeting EGFR and MET, designed to inhibit tumor growth while engaging the immune system.
The National Comprehensive Cancer Network® (NCCN®) Clinical Practice Guidelines in Oncology (NCCN Guidelines®)‡ [19]include amivantamab-vmjw (RYBREVANT) across its FDA-approved treatment settings, including as a Category 1 preferred option in combination with lazertinib (LAZCLUZE) for first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Subcutaneous amivantamab and hyaluronidase-lpuj (RYBREVANT FASPRO) may be substituted for IV amivantamab-vmjw (RYBREVANT®) where appropriate. See the latest NCCN Guidelines® for NSCLC for complete information.§ ||
The NCCN Guidelines for Central Nervous System Cancers also include amivantamab (RYBREVANT)-based regimens, including in combination with lazertinib (LAZCLUZE), as the only NCCN-preferred combination options for patients with EGFR-mutated NSCLC and brain metastases.§ ||
Beyond NSCLC, RYBREVANT-based therapies are being investigated across other solid tumors, including head and neck and colorectal cancers.
The legal manufacturer for RYBREVANT FASPRO and RYBREVANT is Janssen Biotech, Inc.
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.
REFERENCES
[1] Swiecicki, PL, et al. Amivantamab + pembrolizumab + carboplatin in first-line recurrent/metastatic head & neck squamous cell cancer (1L R/M HNSCC) Results from the phase 1b/2 OrigAMI-4 study. Presented at: 2026 European Society for Medical Oncology (ESMO) Congress; October 25, 2026; Madrid, Spain.
[2] ClinicalTrials.gov. A Study of Amivantamab in Addition to Standard of Care Agents (SOC) Compared With SOC Alone in Participants With Recurrent/Metastatic Head and Neck Cancer (OrigAMI-5). https://clinicaltrials.gov/study/NCT07276399?term=origami-5&viewType=Card&rank=1. Accessed October 2026.
[3] Park JC, Ye GH, Merkin R, et al. Outcomes for recurrent or metastatic head and neck cancer by HPV status: a systematic review and meta-analysis. Oncologist. 2025;30(4):oyaf043. doi:10.1093/oncolo/oyaf043
[4] Zebralla V, Wichmann G, Pirlich M, et al. Dysphagia, voice problems, and pain in head and neck cancer patients. Eur Arch Otorhinolaryngol. 2021;278(10):3985-3994. doi:10.1007/s00405-020-06584-6
[5] Nissi L, et al. Recurrence of head and neck squamous cell carcinoma in relation to high-risk treatment volume. Clin Transl Radiat Oncol. 2021;27:139-146. doi:10.1016/j.ctro.2021.01.013
[6] Lee DY, Pan A, Yaskolko M, et al. Real world treatment patterns for recurrent and metastatic head and neck cancer in the post-KEYNOTE 048 era. Front Oncol. 2025;15:1577509. doi: 10.3389/fonc.2025.1577509
[7] Harrington KJ, Rosenberg AJ, Yang MH, et al. Subcutaneous amivantamab in recurrent/metastatic head and neck squamous cell cancer after disease progression on checkpoint inhibitor and chemotherapy: Preliminary results from the phase 1b/2 OrigAMI-4 study. Oral Oncol. 2025;171:107791. doi:10.1016/j.oraloncology.2025.107791
[8] Fasano M, Della Corte CM, Viscardi G et al. Head and neck cancer: the role of anti-EGFR agents in the era of immunotherapy. Ther Adv Med Oncol. 2021;13:1758835920949418.
[9] Cho BC, Simi A, Sabari J, et al. Amivantamab, an epidermal growth factor receptor (EGFR) and mesenchymal-epithelial transition factor (MET) bispecific antibody, designed to enable multiple mechanisms of action and broad clinical applications. Clin Lung Cancer. 2023;24:89–97.
[10] Kalyankrishna S, Grandis JR. Epidermal growth factor receptor biology in head and neck cancer. J Clin Oncol. 2006;24(17):2666-2672.
[11] Cho BC, Lu S, Felip E, et al. Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC. N Engl J Med. 2024;391(16):1486-1498. doi:10.1056/NEJMoa2403614
[12] Yang JCH, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001
[13] Kao H-F, Harrington K, Bhatia A, et al. Amivantamab plus pembrolizumab in previously untreated recurrent/metastatic head and neck squamous cell cancer: Results from the phase 1b/2 OrigAMI-4 study. Clinical Cancer Research. Published online September 15, 2026. doi:10.1158/1078-0432.CCR-26-1372
[14] 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 October 2026.
[15] Barsouk A, Aluru JS, Rawla P, et al. Epidemiology, Risk Factors, and Prevention of Head and Neck Squamous Cell Carcinoma. Med Sci (Basel). 2023;11(2):42. Published 2023 Jun 13. doi:10.3390/medsci11020042
[16] Ghiani L, Chiocca S. High Risk-Human Papillomavirus in HNSCC: Present and Future Challenges for Epigenetic Therapies. Int J Mol Sci. 2022;23(7):3483. https://doi.org/10.3390/ijms23073483
[17] Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for Recurrent Squamous-Cell Carcinoma of the Head and Neck. N Engl J Med. 2016;375(19):1856-1867. doi:10.1056/NEJMoa1602252
[18] Wise-Draper TM, Bahig H, Tonneau M, et al. Current Therapy for Metastatic Head and Neck Cancer: Evidence, Opportunities, and Challenges. Am Soc Clin Oncol Educ Book. 2022;42:1-14. doi:10.1200/EDBK_350442
[19] Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.7.2026 © National Comprehensive Cancer Network, Inc. All rights reserved. Accessed October 2026. To view the most recent and complete version of the guideline, go online to NCCN.org.
[20] RYBREVANT FASPRO [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.
[21] RYBREVANT [Prescribing Information]. Horsham, PA: Janssen Biotech, Inc.