Dr Lim on the Potential Role for Subcutaneous Amivantamab in EGFR-Mutant NSCLC

"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."

Sun-Min Lim, MD, PhD, an associate professor at Severance Hospital within Yonsei University Health System, discussed the potential role for subcutaneous amivantamab-vmjw (Rybrevant) in the first line for advanced EGFR-mutant non–small cell lung cancer (NSCLC) based on results from the phase 2 PALOMA-2 study (NCT05498428).

PALOMA-2 evaluated first-line subcutaneous amivantamab in combination with chemotherapy for patients with advanced NSCLC with EGFR exon 20 insertion mutations. Findings presented at the 2025 IASLC World Conference on Lung Cancer showed that first-line subcutaneous amivantamab plus chemotherapy yielded response rates, duration of response, and survival outcomes consistent with those observed with the intravenous formulation in the phase 3 PAPILLION trial (NCT04538664). 

Among the 63 patients, the objective response rate (ORR) was 76% (95% CI, 64%-86%) by investigator assessment. This compared favorably to PAPILLION's primary analysis ORR of 73% (95% CI, 65%-80%) for intravenous amivantamab plus chemotherapy by blinded independent central review (BICR). The confirmed ORR in PALOMA-2 was 71% (95% CI, 59%-82%) by investigator assessment and 67% (95% CI, 54%-78%) by independent central review (ICR). The clinical benefit rate reached 94% (95% CI, 85%-98%) by investigator assessment and 89% (95% CI, 79%-96%) by ICR. No new safety signals were identified.

Lim explained that PALOMA-2 assessed the feasibility of the subcutaneous formulation across 8 cohorts in various indications, including the first-line and subsequent treatment settings. One key advantage of the subcutaneous formulation is its enhanced tolerability and convenience without sacrificing efficacy, she added. 

In April 2025, the European Commission approved a subcutaneous formulation of amivantamab for use in combination with lazertinib (Lazcluze) for the first-line treatment of adult patients with advanced NSCLC harboring EGFR exon 19 deletions or exon 21 L858R substitution mutations, and as monotherapy for the treatment of adult patients with advanced NSCLC harboring activating EGFR exon 20 insertion mutations after progression on or following platinum-based therapy. Data from the phase 3 PALOMA-3 trial (NCT05388669) supported this regulatory decision.

Lim anticipates that the expanded applicability of these subcutaneous formulations will lead to more future regulatory approvals, increasing their use in clinical practice.