Dr Girard on Updated Data From the PALOMA-2 Trial in EGFR-Mutant NSCLC

“The results are [relatively] impressive. Obviously, this is a phase 2 [trial], but…one hypothesis is that with [the] better safety profile of subcutaneous amivantamab [paired] with the implementation of [a] prophylactic regimen, we [see] prolonged efficacy.”

Nicolas Girard, MD, PhD, head of medical oncology in the Department at Institut Curie, and professor of thoracic oncology and respiratory medicine at the Paris Saclay University, discussed updated data from the phase 2 PALOMA-2 trial (NCT05498428) that were presented at the 2026 European Lung Cancer Congress.

PALOMA-2 evaluated a novel subcutaneous formulation of amivantamab-vmjw (Rybrevant) in combination with lazertinib (Lazcluze) for the first-line treatment of patients with common EGFR-mutated metastatic non–small cell lung cancer (NSCLC). This regimen mirrors the approach used in the phase 3 MARIPOSA trial (NCT04487080), which investigated the intravenous formulation of amivantamab alongside lazertinib.

A key distinction in PALOMA-2 was the use of a subcutaneous delivery method for amivantamab, designed to improve tolerability and patient convenience, Girard explained. Additionally, the study incorporated prophylactic anticoagulation for all enrolled patients, as well as heightened investigator awareness regarding potential cutaneous toxicities. Although formalized prophylactic dermatologic management strategies were not mandated, this proactive awareness likely contributed to improved adverse effect management throughout the study.

Cohort 1 of the trial, which was the focus of the presentation, enrolled 68 patients, and the efficacy outcomes in this cohort were notably strong, Girard said. At a median follow-up of 32.2 months, the combination demonstrated an objective response rate of 85% (95% CI, 75%-93%), with responses occurring rapidly and proving durable over time. At the time of reporting, 44% of patients remained on active treatment, underscoring the regimen’s sustained clinical benefit.

Median progression-free survival (PFS) reached 27.6 months (95% CI, 16.6-33.2), which is numerically higher than what has been previously reported in the MARIPOSA trial. Furthermore, the 18-month overall survival (OS) rate was 88% (95% CI, 77%-94%), highlighting encouraging long-term outcomes in this patient population; OS data remained immature at the time of the presentation.

Although these findings are derived from a phase 2 study, they suggest that the subcutaneous formulation of amivantamab may offer meaningful advantages. One hypothesis is that improved tolerability, potentially driven by both the route of administration and the incorporation of prophylactic measures, may enable patients to remain on therapy longer, thereby enhancing overall efficacy, Girard suggested.

Taken together, the PALOMA-2 results point to a promising evolution of the amivantamab-lazertinib regimen, with the potential to refine first-line treatment strategies for patients with EGFR-mutated advanced NSCLC.