Background
Phase III PALOMA-3 trial; N=657 EGFR-mutant advanced NSCLC after progression on osimertinib; open-label. Compared subcutaneous (SC) vs intravenous (IV) amivantamab, both + lazertinib.
Interventions and follow up
Arm A: SC amivantamab 1400 mg Q3W + lazertinib 240 mg PO daily
Arm B: IV amivantamab 1050 mg (1400 mg if ≥80 kg) Q3W + lazertinib 240 mg PO daily
Primary endpoint: ORR (noninferiority of SC vs IV)
mFollow up: ~8mo
Arm B: IV amivantamab 1050 mg (1400 mg if ≥80 kg) Q3W + lazertinib 240 mg PO daily
Primary endpoint: ORR (noninferiority of SC vs IV)
mFollow up: ~8mo
Results
ORR (SC vs IV): 36% vs 28%, risk difference +8%, 95% CI +0.5 to +15 (meets noninferiority)
mPFS: 6.1 vs 4.3mo, HR 0.86, 95% CI 0.68–1.10
mOS: HR 0.62, 95% CI 0.42–0.92, nominal P=.02
PR: ~35% vs 28%
CR: ~1% vs 0%
mPFS: 6.1 vs 4.3mo, HR 0.86, 95% CI 0.68–1.10
mOS: HR 0.62, 95% CI 0.42–0.92, nominal P=.02
PR: ~35% vs 28%
CR: ~1% vs 0%
Adverse events
Infusion/administration: infusion-related reactions 13% (SC) vs 66% (IV); first-dose administration time ~4.8 min (SC) vs ~5 hr (IV).
Vascular: venous thromboembolism 9% vs 14%.
Other Grade ≥3: ~17% both arms; rash, paronychia, diarrhea comparable.
Vascular: venous thromboembolism 9% vs 14%.
Other Grade ≥3: ~17% both arms; rash, paronychia, diarrhea comparable.
Conclusions
SC amivantamab + lazertinib was noninferior to IV in efficacy, markedly reduced infusion reactions and administration time, and improved convenience — supporting SC as a preferred option in EGFR-mutant NSCLC after osimertinib.
Key Limitations
Open-label; formulation (not new-drug) comparison; OS benefit nominal/exploratory; short follow-up.
Clinical Context
Supported FDA approval of SC amivantamab (2024/2025). SC formulation reduces chair time and infusion reactions vs IV; relevant wherever amivantamab + lazertinib is used post-osimertinib. ESMO recognizes amivantamab-based regimens in this setting.