SC Amivantamab Consistent with IV Formulation in EGFR-Mutated NSCLC

Among all patients treated with the subcutaneous formulation of amivantamab, the objective response rate was 82% per investigator assessment and 87% per independent review committee after a median follow-up of 6.5 months.

First-line subcutaneous amivantamab-vmjm (Rybrevant) exhibited comparable efficacy to intravenous amivantamab when combined with lazertinib (Lazcluze) for the treatment of patients with EGFR-mutated non–small cell lung cancer (NSCLC), according to findings from cohort 5 of the phase 3 PALOMA-2 trial (NCT05498428) presented at the 2025 World Conference on Lung Cancer.1

Among all patients (n = 75) treated with the subcutaneous formulation of amivantamab, the objective response rate (ORR) was 82% (95% CI, 71%-90%) per investigator assessment and 87% (95% CI, 77%-94%) per independent review committee (ICR) after a median follow-up of 6.5 months. Results showed consistency with the phase 3 MARIPOSA trial (NCT04487080) published in the New England Journal of Medicine, which displayed an ORR by blinded independent review committee of 86% (95% CI, 83%-89%) with the intravenous formulation of amivantamab.2

Additionally, the confirmed ORR with the subcutaneous formulation was 79% (95% CI, 69%-88%) per investigator and 83% (95% CI, 73%-91%) per ICR. The confirmed clinical benefit rate (CBR) was 97% (95% CI, 91%-100%) per investigator and 96% (95% CI, 89%-99%) per ICR.

Among responders in the PALOMA-2 trial, the median time to response was 8.1 weeks (range, 7.0-16.5), with a median duration of response (DOR) not reached, with 93% of responses ongoing. Additionally, the median progression-free survival (PFS) and overall survival (OS) were not reached.

“[Patients] receiving frontline amivantamab administered subcutaneously every 4 weeks with lazertinib demonstrated a response rate consistent with those who received the MARIPOSA regimen,” Susan C. Scott, MD, thoracic medical oncologist at the Johns Hopkins Sidney Kimmel Comprehensive Cancer Center and assistant professor of Oncology at Johns Hopkins University School of Medicine, stated in the presentation.1 “There were no new safety signals identified, and there was a 5-fold reduction in the administration-related reactions [ARRs] [with the subcutaneous formulation].”

Investigators in the phase PALOMA-2 trial enrolled patients with treatment-naïve, locally advanced or metastatic NSCLC with documented EGFR exon 19 deletions or L858R mutations with an ECOG performance score of 0 or 1. Patients with brain metastases were permitted if they were stable.

Patients treated received subcutaneous abdominal injections of amivantamab at 1600 mg or 2240 mg if 80 kg or greater for the first cycle and then 3520 mg or 4640 mg if 80 kg or greater thereafter on a schedule of every 4 weeks. Oral lazertinib was given at a dose of 240 mg daily.

The median age was 63 years (range, 31-80), and most patients were female (68%) and Asian (62%). A total of 68% of patients had an ECOG performance score of 1, 32% had a history of smoking, and 43% had brain metastases. Furthermore, 60% vs 40% had exon 19 deletions vs L858R mutations, and all patients had adenocarcinoma histology.

The primary end point of the trial was ORR per investigator assessment. Secondary end points included ORR by ICR, DOR, time to response, CBR, PFS, OS, safety, and pharmacokinetics.

The most common treatment-emergent adverse effects (TEAEs) were EGFR/MET-related. The most common any-grade TEAEs related to EGFR inhibition included paronychia (any-grade, 73%; grade 3 or higher, 5%), rash (58% vs 12%), dermatitis acneiform (40% vs 8%), stomatitis (38% vs 4%), pruritus (34% vs 1%), and diarrhea (29% vs 3%). Associated with MET inhibition, the most common TEAEs included hypoalbuminemia (64% vs 5%) and peripheral edema (36% vs 0%).

Treatment-related AEs leading to discontinuation of all study treatments occurred in 8% of patients, and no prophylactic measures for dermatologic AEs were recommended with PALOMA-2. Additionally, ARRs occurred in 12% (n = 9/77) of patients, of which 78% (n = 7/9) occurred in the first dose.

Additionally, venous thromboembolism (VTE) occurred in 13% of patients, including 10% (n = 7/67) of patients who underwent prophylactic anticoagulation and 30% (n = 3/10) of those who did not. No VTE incidences resulted in dose discontinuation or reduction, or death. One high-grade bleeding event was reported.

References

1. Scott SC, Dias JM, Liu B, et al. PALOMA-2: subcutaneous amivantamab administered every 4 weeks plus lazertinib in first-line EGFR-mutated advanced NSCLC. Presented at: IASLC 2025 World Conference on Lung Cancer. September 6-9, 2025. Barcelona, Spain. Abstract MA08.05
2. 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