Subcutaneous Amivantamab/Lazertinib: a New SOC in EGFR+ NSCLC?

In a conversation with CancerNetwork^®, Nicolas Girard, MD, PhD, spoke about findings from the PALOMA-2 trial (NCT05498428) assessing frontline subcutaneous amivantamab (Rybrevant Faspro) plus lazertinib (Lazcluze) among patients with EGFR-mutated advanced non–small cell lung cancer (NSCLC) that he presented at the 2026 European Lung Cancer Congress.¹ Findings showed that subcutaneous amivantamab plus lazertinib yielded similar efficacy compared with the intravenous formulation of the agent on top of added tolerability and convenience of administration.

According to Girard, head of the Medical Oncology Department at Institut Curie, and professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, the subcutaneous formulation of amivantamab is a “new standard of care” in this population based on data from the PALOMA-2 trial. He noted, however, that it would be necessary to implement various prophylaxis protocols—including those from the SKIPPirr (NCT05663866) study and COCOON study (NCT06120140)—as patients undergo subcutaneous therapy.^2,3

Transcript:

We know that amivantamab plus lazertinib is a new standard of care for the first-line treatment of patients with metastatic EGFR-mutated NSCLC. In the landmark trial, MARIPOSA [NCT04487080] amivantamab was delivered intravenously. Obviously, the intravenous injection is a burden, not only for the patients who have to come to the hospital to receive the drug, but also for the health care system at the hospital. We also know that subcutaneous amivantamab is [performing] similarly to [intravenous] amivantamab based on the PALOMA-3 [NCT05388669] randomized phase 3 study in the late-line setting in terms of pharmacokinetics and efficacy. It was straightforward to move to subcutaneous amivantamab assessment in the first-line setting in combination with lazertinib.

This is the way to move forward with the amivantamab/lazertinib combination. [Subcutaneous amivantamab], to me, is a new standard of care. It is a way to organize from the initiation of treatment and the administration of amivantamab. We still need to continue to implement the prophylactic measures: SKIPPirr for the administration-related reactions, COCOON for the dermatologic [adverse] effects—there are new modalities within COCOON that are currently being tested—and the prophylactic anti coagulation.

References

1. Girard N, Nagasaka M, Dias JM, et al. First-line subcutaneous amivantamab plus lazertinib in EGFR-mutated advanced NSCLC: updated results from the PALOMA-2 study. Presented at the 2026 European Lung Cancer Congress; March 25-28, 2026; Copenhagen, Denmark. Abstract 13P.
2. Spira AI, Paz-Ares L, Han JY, et al. Preventing infusion-related reactions with intravenous amivantamab-results from SKIPPirr, a phase 2 study: a brief report. J Thorac Oncol. 2025;20(6):809-816. doi:10.1016/j.jtho.2025.01.018
3. Cho BC, Li W, Spira AI, et al. Enhanced versus standard dermatologic management with amivantamab-lazertinib in EGFR-mutated advanced NSCLC: the COCOON global randomized controlled trial. J Thorac Oncol. 2025;20(10):1517-1530. doi:10.1016/j.jtho.2025.07.117.