Sub-Q Amivantamab and Supportive Care Minimize Discontinuation in EGFR+ NSCLC

Subcutaneous amivantamab (Rybrevant Faspro) plus lazertinib (Lazcluze), given with prophylactic supportive care, was associated with low rates of key treatment-related adverse events (AEs) including rash, administration-related reactions (ARRs), and venous thromboembolism (VTE) with extended follow-up in patients with previously untreated, EGFR-mutated advanced non–small cell lung cancer (NSCLC), according to data presented at the 2026 International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer (WCLC).¹

The findings come from cohort 1 of the open-label, single-arm, phase 2b COPERNICUS study (NCT06667076), which is evaluating subcutaneous amivantamab dosed once every 4 weeks plus lazertinib, with prophylactic anticoagulation and enhanced dermatologic supportive care, in the first-line setting.

“[Amivantamab] plus [lazertinib] has already shown that patients with EGFR-mutated lung cancer can live longer, and these latest results mark an important evolution in the treatment approach,” Balazs Halmos, MD, MS, director of thoracic oncology and associate director of clinical science at Montefiore Einstein Comprehensive Cancer Center, stated in a news release.² “With subcutaneous administration, less frequent dosing and prophylactic strategies, the regimen has been developed with the treatment experience in mind, helping patients start treatment and stay on it.”

Trial Design and Safety Findings

COPERNICUS is a pragmatic, single-arm study with a target US enrollment of 300 previously untreated patients, designed to reflect everyday clinical practice. It is enrolling at both academic and community sites, permitting 1 cycle of first-line chemotherapy with streamlined radiology requirements, and is meant to reduce visit frequency through every-4-weeks amivantamab dosing.

Patients received prophylactic anticoagulation during the first 4 months of treatment and an enhanced dermatologic supportive-care regimen aligned with that used in the phase 3 COCOON trial (NCT06120140),³ which included oral doxycycline or minocycline, clindamycin 1%, chlorhexidine 4%, and ceramide-based moisturizer. The analysis reported on 214 US patients who received the regimen with COCOON-aligned dermatologic prophylaxis and anticoagulation; the median age was 67 years, and 22% were 75 years or older. Twenty-seven percent of patients were Asian, 10% were African American, and 10% were Hispanic/Latino.

At a median follow-up of 8.3 months, the majority of AEs were grade 1 or 2, with no new safety signals reported. Rash occurred in 25% of participants, and ARRs and VTE were each reported in 3%. Overall, 8% of participants discontinued treatment because of AEs; no patients discontinued because of ARRs, and 1% discontinued because of rash or VTE.

Comparison With Intravenous Amivantamab in MARIPOSA

Intravenous (IV) amivantamab plus lazertinib previously demonstrated a statistically significant overall survival benefit over osimertinib (Tagrisso) in the first-line EGFR-mutated advanced NSCLC population in the phase 3 MARIPOSA trial (NCT04487080) with an HR of 0.75 (P = .005).⁴

The phase 3 PALOMA-3 study found the subcutaneous formulation of amivantamab noninferior to IV formulation, which led to the FDA approval of the subcutaneous versionin December 2025.⁵

The COPERNICUS investigators cited that AEs with the IV regimen were most common during the first 4 months of treatment and included ARRs in 55% of patients, rash in 55%, and VTE in 23% in this period and 63%, 63%, and 37% overall, respectively; 34% of patients discontinued treatment because of AEs, including 5% because of ARRs and 3% because of VTE.^1,2,4 The numerically lower AE and discontinuation rates observed with subcutaneous amivantamab in COPERNICUS were attributed by the study authors to the subcutaneous formulation, less frequent dosing, and the added VTE and dermatologic prophylaxis, though the 2 approaches were not directly compared in a randomized population.

REFERENCES

1. Halmos B, Tu J, Goldberg SB, et al. Subcutaneous amivantamab + lazertinib with supportive care in EGFR-mutant NSCLC: longer follow-up from the pragmatic COPERNICUS study. Presented at: IASLC 2026 World Conference on Lung Cancer; 2026; Seoul, South Korea. Abstract M012.09.

2. RYBREVANT FASPRO™ (amivantamab and hyaluronidase-lpuj) plus LAZCLUZE® (lazertinib) with prophylactic strategies shows low rates of treatment-related events at WCLC 2026. News release. Johnson & Johnson. September 14, 2026. Accessed September 16, 2026. https://tinyurl.com/3b9rcuej

3. Yang JC, Lu S, Hayashi H, et al; MARIPOSA Investigators. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001

4. Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530. doi:10.1016/j.jtho.2025.07.117

5. FDA approves amivantamab and hyaluronidase-lpuj for subcutaneous injection. News release. US FDA. December 17, 2025. Accessed September 17, 2026. https://tinyurl.com/3fr3nh9y