The phase 2 PALOMA-2 bridging study has reinforced the therapeutic potential of subcutaneous amivantamab plus chemotherapy in patients with EGFR exon 20 insertion-mutated advanced non-small cell lung cancer (NSCLC), delivering efficacy and safety profiles consistent with the established intravenous formulation. Results were presented at the 2025 World Lung Cancer Conference in Barcelona, Spain.
Primary Efficacy Outcomes
Among 66 patients enrolled in PALOMA-2, the objective response rate (ORR) reached 76% by investigator assessment, closely matching the 73% ORR observed with intravenous amivantamab plus chemotherapy in the pivotal phase 3 PAPILLON study. The confirmed ORR was 71% by investigator assessment and 67% by independent central review.
"These findings are very similar and consistent with the PAPILLON study results," said Sun Min Lim, MD, PhD, of the Division of Medical Oncology at Yonsei University College of Medicine in Seoul, South Korea, who presented the data.
The clinical benefit rate reached an impressive 94% by investigator assessment and 89% by independent central review. The median time to response was within 2 months, and at the time of data cutoff, most patients maintained ongoing responses.
Survival and Safety Profile
At a median follow-up duration of just over 10 months, the median progression-free survival was 12.2 months. Median overall survival was not estimable at the time of data cutoff, indicating sustained clinical benefit in this patient population with historically limited therapeutic options.
The safety profile remained consistent with previous studies, with no new safety signals identified. According to Lim, the subcutaneous formulation offers "enhanced tolerability and convenience without sacrificing efficacy" compared to intravenous administration.
Regulatory Landscape and Clinical Impact
The European Commission granted approval in April 2025 for subcutaneous amivantamab formulations, supported by data from the phase 3 PALOMA-3 trial. The approval covers combination therapy with lazertinib for first-line treatment of advanced NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations, as well as monotherapy for EGFR exon 20 insertion mutations after platinum-based therapy progression.
"These subcutaneous formulations will be expanding the applicability of amivantamab in EGFR-mutant NSCLC. We expect more approvals by different regulatory entities in the future," Lim noted.
Study Design and Patient Population
PALOMA-2 evaluated the subcutaneous formulation across 8 cohorts in various clinical scenarios, including first-line and subsequent treatment settings. The study specifically targeted patients with EGFR exon 20 insertion-mutated advanced NSCLC, a population with historically poor outcomes and limited treatment options.
The consistent efficacy demonstrated across both intravenous and subcutaneous formulations suggests that the route of administration does not compromise therapeutic benefit while potentially improving patient experience and clinical workflow efficiency.
