Rybrevant Faspro (amivantamab and hyaluronidase-lpuj) / J&J, Halozyme - LARVOL DELTA

First-Line Subcutaneous Amivantamab Plus Chemotherapy in EGFR Exon 20 Insertion-Mutated Advanced NSCLC: Results From PALOMA-2 (IASLC-WCLC 2025) - P2 | "Introduction : Intravenous amivantamab plus chemotherapy (carboplatin-pemetrexed)is approved for first-line treatment of patients with EGFR exon 20 insertion(Ex20ins)-mutated advanced non-small cell lung cancer (NSCLC), based on the resultsof the PAPILLON study. Discontinuationof amivantamab due to treatment-related AEs was 12%. Conclusions : Among participants with EGFR Ex20ins-mutatedadvanced NSCLC, first-line treatment with subcutaneous amivantamab Q3W plus chemotherapydemonstrated a response rate and safety profile consistent with historical intravenousamivantamab Q3W data, with a reduced incidence of ARRs."

Clinical • EGFR exon 20 • Metastases • Lung Cancer • Neutropenia • Non Small Cell Lung Cancer • Solid Tumor • EGFR

PALOMA-2: Subcutaneous Amivantamab Administered Every 4 Weeks Plus Lazertinib in First-Line EGFR-Mutated Advanced NSCLC (IASLC-WCLC 2025) - P2 | "In MARIPOSA (median follow-up, 22.0 months), intravenous amivantamab administered every 2 weeks (Q2W) plus lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib (hazard ratio, 0.70; P <0.001). Conclusions : In participants with EGFR- mutated advanced NSCLC, first-line treatment with subcutaneous amivantamab Q4W plus lazertinib showed a response rate similar to historical intravenous amivantamab Q2W data with fewer ARRs; incidence of VTEs was low with prophylactic anticoagulation. The subcutaneous amivantamab Q4W regimen will potentially further improve patient convenience and overall treatment experience."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Amivantamab plus paclitaxel in recurrent/metastatic (R/M) head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition: Identification of the recommended combination dose from the phase Ib/II OrigAMI-4 study (ESMO 2025) - P1/2 | "Conclusions Ami + paclitaxel was shown to be safe, with no new safety signals identified. The combination showed rapid and meaningful antitumor activity in pts with HPV-unrelated, previously treated R/M HNSCC after disease progression on checkpoint inhibition."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Amivantamab in recurrent/metastatic head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition and chemotherapy: Results from the phase Ib/II OrigAMI-4 study (ESMO 2025) - P1/2 | "Conclusions Amivantamab demonstrated rapid and meaningful antitumor activity in pts with HPV-unrelated, previously treated R/M HNSCC after disease progression on checkpoint inhibition and chemotherapy. The early safety profile was consistent with prior studies, with no new safety signals identified."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

First-line Subcutaneous Amivantamab Plus Lazertinib in EGFR-mutated Advanced NSCLC: Updated Results From the PALOMA-2 study (ELCC 2026) - No abstract available

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Subcutaneous amivantamab vs intravenous amivantamab, both in combination with lazertinib, in refractory EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Primary results, including overall survival (OS), from the global, phase 3, randomized controlled PALOMA-3 trial. (ASCO 2024) - P3 | "PALOMA-3 (NCT05388669) evaluated SC ami+laz vs IV ami+laz for pharmacokinetics (PK), efficacy, and safety among pts with EGFR Ex19del or L858R-mutated advanced NSCLC and disease progression on osimertinib and platinum-based chemotherapy. SC ami demonstrated noninferior PK and ORR compared to IV. Unexpectedly, DoR, PFS, and OS were longer in the SC arm vs IV, suggesting that the route of administration or formulation may affect outcomes. The safety profile was improved for SC ami, with lower IRR and VTE rates."

Clinical • Combination therapy • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

A phase 2b study of subcutaneous amivantamab with lazertinib as first-line treatment, or with chemotherapy as second-line treatment, for EGFR-mutated non-small cell lung cancer (NSCLC): COPERNICUS (AACR 2025) - P2 | "In Cohort 1, participants must not have received any prior systemic therapy and will receive SC amivantamab and oral lazertinib; in Cohort 2, participants must have had disease progression after EGFR-TKI monotherapy and will receive SC amivantamab and chemotherapy (carboplatin-pemetrexed). COPERNICUS aims to evaluate the efficacy and safety of SC amivantamab regimens using a pragmatic study design to enroll participants with diverse backgrounds and combine advancements in supportive care to prevent and proactively manage AEs."

Clinical • P2b data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Subcutaneous amivantamab (ami) in patients (pts) with advanced solid malignancies: The PALOMA study—Updated safety and identification of the recommended phase 2 dose. (ASCO 2023) - P1b | "Ami SC was well tolerated with meaningful reductions in administration time and TEAEs. Ami SC provided a quantitative and qualitative improvement in the symptoms of IRRs vs historical IV rates. The identified RP2D for ami SC on the Q2W schedule achieved similar exposure as the approved IV dose."

Clinical • Metastases • P2 data • Cardiovascular • Hypertension • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Solid Tumor

Subcutaneous amivantamab administered every 4 weeks (Q4W) in patients with advanced solid malignancies: The phase Ib PALOMA study (ELCC 2024) - P2 | "Conclusions Ami SC Q4W had lower rates of IRRs and was better tolerated vs ami IV. The ami SC Q4W dose of 3520 mg (≥80 kg: 4640 mg) achieved comparable exposure to the approved IV dose and is being further evaluated in the phase II, PALOMA-2 (NCT05498428) study."

Clinical • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Subcutaneous amivantamab and lazertinib as first-line treatment in patients with EGFR-mutated, advanced non-small cell lung cancer (NSCLC): Results from the phase 2 PALOMA-2 study. (ASCO 2024) - P2 | "IV ami + lazertinib (laz), a 3 rd -generation EGFR TKI, demonstrated superior progression-free survival (PFS) in patients (pts) with treatment-naïve, advanced EGFR-mutated NSCLC vs osimertinib (Cho AnnOncol 2023). SC ami+laz showed a response rate similar to historic IV ami+laz in first-line EGFR-mutated NSCLC, with an improved safety profile that included significantly lower ARR rates. Further, prophylactic anticoagulation can be safely implemented and reduced incidence of VTE."

Clinical • Late-breaking abstract • Metastases • P2 data • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism • EGFR

Subcutaneous versus Intravenous Amivantamab, both in Combination with Lazertinib, in Refractory EGFR-mutated NSCLC: Primary Results from the Phase 3 PALOMA-3 Study. (PubMed, J Clin Oncol) - "Subcutaneous amivantamab-lazertinib demonstrated noninferiority to intravenous amivantamab-lazertinib, offering a consistent safety profile with reduced infusion-related reactions, increased convenience, and prolonged survival."

Combination therapy • Journal • P3 data • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism • EGFR

Subcutaneous vs Intravenous Amivantamab: Patient Satisfaction and Resource Utilization Results from the PALOMA-3 Study (IASLC-WCLC 2024) - P3 | "Methods : 418 patients with EGFR -mutated advanced NSCLC whose disease progressed on osimertinib and platinum-based chemotherapy were randomized 1:1 to subcutaneous (n=206) or intravenous amivantamab (n=212), both with lazertinib. Conclusions : Intravenous amivantamab has demonstrated superior efficacy across multiple patient populations. Subcutaneous amivantamab provides the additional advantages of lower resource utilization and significantly higher patient satisfaction, and offers a convenient mode of administration for patients and healthcare providers, improving overall treatment experience."

Clinical • HEOR • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pain • Solid Tumor • Thoracic Cancer • EGFR

Subcutaneous Immunotherapy in Cancer: Where We Are Now, What It Changes, and What to Watch Next. (PubMed, JCO Oncol Pract) - "Regulatory approvals now include SC atezolizumab and nivolumab across broad indications, SC amivantamab in Europe, and SC pembrolizumab following positive phase III results. The integration of SC immunotherapy into routine practice may improve patient experience, alleviate pressure on oncology services, and reduce health system costs without compromising outcomes. Future research should focus on implementation, real-world cost-effectiveness, and the potential for SC combinations in multiagent regimens."

Journal • Review • Oncology

Received manufacturing and marketing approval for Rybrofaz combination subcutaneous injection, a subcutaneous formulation of Rybrevant [Google translation] (J&J Press Release) - "This approval is based on the results of the global Phase III study PALOMA-3 (NCT05388669) and the global Phase II study PALOMA-2 (NCT05498428), which demonstrated that Rybrofaz is expected to have similar efficacy to Rybrevant."

Japan approval • Non Small Cell Lung Cancer

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) and the NCCN Guidelines Navigator for Non-Small Cell Lung Cancer, Version 3.2026. (NCCN)

NCCN guideline • Non Small Cell Lung Cancer

Johnson & Johnson…announced today that the U.S. Food and Drug Administration (FDA) approved RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj), the first and only subcutaneously (SC) administered therapy for patients with epidermal growth factor receptor (EGFR)-mutated non-small cell lung cancer (NSCLC) (PRNewswire) - "RYBREVANT FASPRO is approved across all indications of RYBREVANT (amivantamab-vmjw)....Approval builds on previously reported Phase 3 MARIPOSA data showing unmatched overall survival benefit of this chemotherapy-free regimen, projected to exceed four years."

FDA approval • Non Small Cell Lung Cancer

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. (PubMed, Oral Oncol) - P1/2 | "Subcutaneous amivantamab as second-/third-line treatment among participants with R/M HNSCC demonstrated rapid and durable antitumor activity. The safety profile of subcutaneous amivantamab was consistent with previous studies."

Checkpoint inhibition • Journal • P1/2 data • Head and Neck Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck

Amivantamab in recurrent/metastatic head & neck squamous cell cancer (HNSCC) after disease progression on checkpoint inhibition and chemotherapy: Results from the phase 1b/2 OrigAMI-4 study (JADPRO 2025) - "Subcutaneous amivantamab plus pembrolizumab and carboplatin is proceeding to first-line, phase 3 development in the OrigAMI-5 trial. Background Cetuximab monotherapy demonstrated response rates of up to 24% among participants with human papillomavirus (HPV)-unrelated R/M HNSCC after disease progression on checkpoint inhibitor and platinum-based chemotherapy...Figure 3: Rapid antitumor activity (CT scans showing reduction in tumor mass at week 7). Figure 4: Durability of response – 46% remained on treatment at data cut-off."

Checkpoint inhibition • IO biomarker • Metastases • P1/2 data • Dental Disorders • Fatigue • Head and Neck Cancer • Hypopharyngeal Cancer • Oncology • Squamous Cell Carcinoma • Squamous Cell Carcinoma of Head and Neck • Stomatitis

COPERNICUS: A multinational pragmatic phase II trial of subcutaneous (SC) amivantamab (Ami) in common EGFR-mutated (cEGFRm) NSCLC (ESMO 2025) - P2 | "Background In advanced c EGFR m (exon 19 deletion/exon 21 L858R substitution) NSCLC, intravenous (IV) ami is FDA-/EMA-approved combined with lazertinib (laz) for first-line (1L), and with carboplatin-pemetrexed (chemo) for second-line (2L) treatment. Legal entity responsible for the study Johnson & Johnson. Funding Johnson & Johnson."

P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Subcutaneous (SC) amivantamab (ami) plus chemotherapy (chemo) in EGFR-mutant (EGFRm) advanced non-small cell lung cancer (NSCLC) after disease progression on osimertinib (osi) (ESMO 2025) - P2 | "Carboplatin was given up to 4 cycles, and pemetrexed until disease progression. Ami discontinuation due to treatment-related AEs was 5%. Conclusions In pts with EGFR m advanced NSCLC post-osi, ami SC Q3W + chemo had a response rate and safety profile consistent with historical ami IV Q3W + chemo, with fewer ARRs."

Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Subcutaneous (SC) after intravenous (IV) amivantamab in advanced NSCLC: Initial results from PALOMA-2 (JADPRO 2025) - P1/2 | "The safety profile of participants who switched to amivantamab SC with lazertinib from IV AMV to SC AMV therapy was consistent with the profile previously observed with AMV SC monotherapy, demonstrating that the IV to SC switch occurred safely. Most participants were satisfied with AMV SC with or without rHuPH20, found it convenient, and preferred it over prior intravenous IV AMV."

Metastases • Fatigue • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

PALOMA-2: Initial Report Details Patient Experiences of Subcutaneous Amivantamab After IV Administration in Advanced EGFR-Mutated NSCLC (Cancer Nursing Today) - "The median duration of treatment was 3.1 months for IV administration and 7.4 months for subcutaneous administration. The median follow-up from the first subcutaneous dose was 9.7 months....In addition, most adverse events were graded between 1 and 2, and the most common adverse events included paronychia (44%), rash (40%), and hypoalbuminemia (40%). Only one patient discontinued treatment due to the toxicity of interstitial lung disease."

P2 data • Non Small Cell Lung Cancer

Subcutaneous amivantamab delivers promising 45 percent overall response rate with median duration of 7.2 months in recurrent or metastatic head and neck cancer (PRNewswire) - "Data were presented during a mini-oral session at the European Society for Medical Oncology (ESMO) 2025 Congress....In Cohort 1 of the OrigAMI-4 study, treatment with SC amivantamab resulted in an overall response rate (the primary endpoint) of 45 percent in 38 efficacy-evaluable patients with R/M HNSCC unrelated to HPV with disease progression on or after a PD-1 or PD-L1 checkpoint inhibitor and platinum-based chemotherapy (95 percent confidence interval [CI], 29-62)....Median progression-free survival was 6.8 months (95 percent CI, 4.2-9.0)....Based on these results, Johnson & Johnson is initiating further study of SC amivantamab in head and neck cancer with the Phase 3 OrigAMI-5 study..."

New P3 trial • P1/2 data • Squamous Cell Carcinoma of Head and Neck

PALOMA-2: A Study of Amivantamab in Participants With Advanced or Metastatic Solid Tumors Including Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (clinicaltrials.gov) - P2 | N=520 | Recruiting | Sponsor: Janssen Research & Development, LLC | N=390 ➔ 520

Enrollment change • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

The Phase 2b COPERNICUS Study of Subcutaneous Amivantamab with Lazertinib as First-Line Treatment, or with Chemotherapy as Second-Line Treatment, for EGFR-Mutated Non-Small Cell Lung Cancer: a Vodcast. (PubMed, Oncol Ther) - P2 | "COPERNICUS uses a pragmatic study design to evaluate the efficacy and safety of subcutaneous amivantamab regimens combined with advancements in supportive care to prevent and proactively manage AEs in a diverse participant population. Supplementary file1 (MP4 117333 KB)."

Journal • P2b data • Cardiovascular • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Venous Thromboembolism • EGFR