The U.S. Food and Drug Administration (FDA) has approved a new, simplified monthly dosing schedule* for amivantamab and hyaluronidase (Rybrevant Faspro™; Johnson & Johnson)^.
When administered in combination with oral lazertinib (Lazcluze®; Johnson & Johnson) for the first-line treatment of epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer (NSCLC), monthly dosing delivers outcomes consistent with those of the previously approved bi-weekly subcutaneous (SC) dosing schedule. Monthly dosing also reduces treatment visits while maintaining established safety and efficacy [1]
This milestone builds on the FDA approval, in December 2025, of amivantamab and hyaluronidase, which reduced administration time from hours to minutes and offers a fivefold reduction in administration-related reactions (ARRs) compared with intravenous (IV) delivery. [2][3][4][5] With this newly approved monthly dosing schedule, patients can transition to monthly dosing as early as Week 5. Together, these advances build on an unmatched survival benefit while supporting continued treatment optimization, further simplifying care delivery, and offering greater convenience.[1]
“A monthly dosing schedule offers patients convenience without sacrificing efficacy,” said Danny Nguyen, M.D., Assistant Clinical Professor, Department of Medical Oncology & Therapeutics Research, City of Hope, and principal investigator for the PALOMA-2 NCT05498428) trial** and the MARIPOSA (NCT04487080) study.***
“With a flexible schedule that reduces time in the clinic, patients may be able to stay on therapy longer and free up time to focus on the moments that matter most.”
Non-Small Cell Lung Cancer
Worldwide, lung cancer is one of the most common cancers, with NSCLC making up 80% to 85% of all lung cancer cases.[6][7] The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.[7] Among the most common driver mutations in NSCLC are alterations in EGFR, a receptor tyrosine kinase that controls cell growth and division.[8] EGFR mutations are present in 10% to 15% of Western patients with NSCLC and adenocarcinoma histology, and in 40% to 50% of Asian patients. [7][8][10][11] EGFR exon 19 deletions or EGFR L858R mutations are the most common EGFR mutations. [12][13] The five-year survival rate for all patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20%.[14] EGFR exon 20 insertion mutations are the third-most prevalent activating EGFR mutations.[15] Patients with EGFR exon 20 insertion mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than that of patients with EGFR exon 19 deletions or L858R mutations, who have a real-world five-year OS of 19%. [13]
EGFR Mutations
Epidermal growth factor receptor (EGFR) mutations are among the most common oncogenic drivers in NSCLC, especially in younger individuals and those who have never smoked. These mutations promote uncontrolled cell growth and are linked to poor outcomes.[11] Despite progress with targeted therapies, including third-generation EGFR TKI, long-term survival remains limited, with five-year survival rates below 20 percent.[14] Overcoming resistance mechanisms, such as MET amplification and secondary EGFR mutations, is essential for improving outcomes and extending survival in EGFR-mutated NSCLC. [16]
Combination of Monthly dosing
Recently presented at the World Conference on Lung Cancer (WCLC), held September 6-9, 2025, in Barcelona, Spain, the PALOMA-2 study data demonstrated that monthly amivantamab and hyaluronidase dosing in combination with lazertinib delivered a high objective response rate (ORR) in previously untreated, EGFR-mutated advanced NSCLC. The study showed a significant reduction in ARRs compared to historical IV administration and consistent rates with bi-weekly SC delivery.[2]
“This latest milestone represents the culmination of our unwavering efforts and commitment to fundamentally redefine the way we treat patients with EGFR-mutated non-small cell lung cancer,” said Mahadi Baig, M.D., M.H.C.M., Vice President, U.S. Medical Affairs, Johnson & Johnson.
“Building on unmatched overall survival and regimens that support proactive side effect management, this once-monthly injection now delivers the simplest and fastest combination therapy for patients with EGFR-mutated non-small cell lung cancer.”
The safety profile of monthly dosing with amivantamab and hyaluronidase is comparable to that of every-two-week dosing. Consistent with IV and SC administration, most adverse events were related to EGFR/MET inhibition. ARRs were consistent with the bi-weekly dosing schedule (12% vs 13%, respectively) and were fivefold lower than historical IV administration (66%). Similarly, venous thromboembolic events (VTEs) were consistent with bi-weekly SC administration (13% vs 11% with anticoagulation) and lower than historic IV data without anticoagulation (38%). [1][2]
No new safety signals were identified. Only 8% of patients discontinued amivantamab due to treatment-related adverse events. The mean plasma concentration levels were consistent with historical IV and bi-weekly SC dosing data, supporting pharmacokinetic comparability. [2]
Third-generation tyrosine kinase inhibitors
Resistance to third-generation tyrosine kinase inhibitors (TKIs), such as osimertinib (when given alone or with chemotherapy), remains a major barrier to long-term disease control.[17] The combination regimen of amivantamab (Rybrevant®; Johnson & Johnson) plus lazertinib uses a multitargeted mechanism of action: targeting EGFR mutations from two angles, blocking MET, and engaging the immune system.[20] This approach has the potential to alter the natural history of the disease by narrowing the spectrum and simplifying the mechanisms of acquired resistance. [20]
An analysis from MARIPOSA, presented at the International Association for the Study of Lung Cancer (IASLC) 2025 World Congress on Lung Cancer (WCLC), demonstrated that the combination significantly reduced the development of EGFR– and MET-driven resistance compared with osimertinib in the first-line setting. MET amplifications occurred in 3% of patients on the combination vs 13% on osimertinib (P=0.002), and secondary EGFR mutations (such as C797S) were significantly lower with RYBREVANT® plus lazertinib (1% vs 8%; P=0.01). Notably, acquired MET amplification led to early discontinuation in 23 percent of patients on osimertinib within six months, compared with four percent on RYBREVANT® plus lazertinib, [19][20]
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Note:^ Amivantamab and hyaluronidase (Rybrevant Faspro™) is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s Enhanze® drug delivery technology.
* Once-monthly dosing to begin at week 5 onward. Weekly injections are administered between weeks 1 and 4.
** The PALOMA-2 trial (NCT05498428) is an open-label Phase 2 study evaluating the efficacy, safety, and pharmacokinetics (PK) of first-line SC amivantamab (administered via manual injection) combined with lazertinib and/or chemotherapy in patients with EGFR-mutated advanced or metastatic NSCLC. The primary endpoint was ORR as assessed by the investigator per RECIST v1.1. [2][6] PALOMA-2 Cohort 5 evaluated the efficacy, PK, and safety of first-line SC amivantamab Q4W plus lazertinib in EGFR-mutated NSCLC.
*** MARIPOSA (NCT04487080), which enrolled 1,074 patients, is a randomized, Phase 3 study evaluating RYBREVANT® (amivantamab-vmjw) plus lazertinib versus osimertinib and versus lazertinib alone in first-line treatment of patients with locally advanced or metastatic NSCLC with EGFR ex19del or substitution mutations. The primary endpoint of the study is PFS (using RECIST v1.1 guidelines) as assessed by Blinded Independent Central Review (BICR). Secondary endpoints include overall survival (OS), ORR, duration of response (DoR), progression-free survival after first subsequent therapy (PFS2), and intracranial PFS.[20]
# In 2018, Janssen Biotech entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib (marketed as LECLAZA in South Korea). Lazertinib is an oral, third-generation, brain-penetrant EGFR TKI that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. An analysis of the efficacy and safety of lazertinib from the Phase 3 LASER301 study was published in The Journal of Clinical Oncology in 2023.
Clinical trials
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) – ClinicalTrials.gov ID NCT05498428
A Study of Amivantamab and Lazertinib Combination Therapy Versus Osimertinib in Locally Advanced or Metastatic Non-Small Cell Lung Cancer (MARIPOSA) – ClinicalTrials.gov ID NCT04487080
Highlights of Prescribing Information
Amivantamab and hyaluronidase (Rybrevant Faspro™; Johnson & Johnson) [Prescription Information]
References
[1] Scott S, et al. PALOMA-2: Subcutaneous Amivantamab Administered Every 4 Weeks Plus Lazertinib in First-Line EGFR-Mutated Advanced NSCLC. Abstract presented at: International Association for the Study of Lung Cancer at the 2025 World Conference on Lung Cancer (WCLC); September 9, 2025; Barcelona, Spain.
[2] George S, et al. Systematic literature review of intravenous versus subcutaneous administration of oncology therapies: A clinical, economic, and patient perspective. Cancer Treatment Reviews. 2025 Sep; 139(102974):1-13.
[3] Bittner B, et al. Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities. BioDrugs. 2018 Oct;32(5):425-440.
[4] Aguiar-Ibáñez R, et al. Differences Between Intravenous and Subcutaneous Modes of Administration in Oncology from the Patient, Healthcare Provider, and Healthcare System Perspectives: A Systematic Review. Adv Ther. 2024 Dec;41(12):4396-4417.
[5] Epstein R S, et al. Cancer patients’ perspectives: A qualitative study of reasons for subcutaneous preference vs intravenous treatment. Abstract presented at: 2025 ASCO Annual Meeting; May 28, 2025; Chicago.
[6] Hayashi H, et al. Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA [IASLC abstract PT1.03.06]. Presented at: IASLC 2025 World Lung Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain.
[7] Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line EGFR-mutant Advanced NSCLC – Final Overall Survival from MARIPOSA [ELCC abstract #40]. Presented at: 2025 European Lung Cancer Congress (ELCC); March 26-29, 2025; Paris, France.
[8] Oxnard GR, Lo PC, Nishino M, et al. Natural history and molecular characteristics of lung cancers harboring EGFR exon 20 insertions. J Thorac Oncol. 2013;8(2):179-184. doi:10.1097/JTO.0b013e3182779d18.
[9] Hayashi H, et al. Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA [IASLC abstract PT1.03.06]. Presented at: IASLC 2025 World Lung Conference on Lung Cancer; September 6-9, 2025; Barcelona, Spain.
[10] Hayashi H, et al. Mechanisms of Acquired Resistance to First-Line Amivantamab Plus Lazertinib Vs Osimertinib: Updated Analysis from MARIPOSA. Poster presented at: IASLC 2025 World Conference on Lung Cancer (WCLC); September 6-9, 2025; Barcelona, Spain.
[11] The World Health Organization. Lung Cancer. Accessed July 2025. https://www.who.int/news-room/fact-sheets/detail/lung-cancer
[12] American Cancer Society. What is Lung Cancer? Accessed July 2025. https://www.cancer.org/content/cancer/en/cancer/lung-cancer/about/what-is.html
[13] Melosky B, et al. Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis. Mol Diagn Ther. 2021 Nov 23;26(1):7-18.
[14] 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.
[15] 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.
[16] American Cancer Society. Personalized care for patients with EGFR-mutant nonsmall cell lung cancer: Navigating early to advanced disease management. Accessed November 2025. https://acsjournals.onlinelibrary.wiley.com/doi/10.3322/caac.70024
[17] American Lung Association. EGFR and Lung Cancer. Accessed July 2025. https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing
[18] Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore.
[19] 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.
[20] Arcila M, et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9.
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DOI
 has approved a new, simplified monthly dosing schedule* for amivantamab and hyaluronidase (Rybrevant Faspro™; Johnson & Johnson)^.){kind=link}