Subcutaneous Amivantamab is a ‘Way to Move Forward’ in EGFR+ NSCLC Care

In a conversation with CancerNetwork^®, Nicolas Girard, MD, PhD, detailed the results and clinical implications of the PALOMA-2 trial (NCT05498428), evaluating subcutaneous amivantamab (Rybrevant Faspro) in combination with lazertinib (Lazcluze) for patients with advanced non–small cell lung cancer (NSCLC) harboring EGFR mutations. According to data that he and colleagues presented in a poster session at the 2026 European Lung Cancer Congress, treatment with subcutaneous amivantamab demonstrated consistent efficacy compared with the agent’s intravenous formulation, while exhibiting the added tolerability and convenience benefits of subcutaneous administration.¹

Girard, head of the Medical Oncology Department at Institut Curie, and professor of Thoracic Oncology and Respiratory Medicine at the Paris Saclay University, stated that subcutaneous administration is the “way to move forward” with the amivantamab/lazertinib regimen, which represents a new standard of care in the field. Looking ahead, he also described how other therapies like datopotamab deruxtecan-dlnk (Datroway) and sacituzumab govitecan-hziy (Trodelvy) may represent potential next steps for offering more therapeutic choices to patients.

CancerNetwork: What was the rationale for evaluating subcutaneous amivantamab plus lazertinib among patients with EGFR-mutated advanced NSCLC?

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 [phase 3 MARIPOSA trial (NCT04487080)], amivantamab was delivered intravenously.² 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 [phase 3 PALOMA-3 trial (NCT05388669)] randomized phase 3 study, in the late-line setting in terms of pharmacokinetics and efficacy.³ It was straightforward to move to subcutaneous amivantamab assessment in the first-line setting in combination with lazertinib.

What do current efficacy data show regarding the potential utility of this subcutaneous amivantamab combination?

With subcutaneous amivantamab every 2 weeks plus lazertinib, we see a response rate of 85% and a median PFS above 26 months, which is higher than what we have in MARIPOSA. This may be a matter of selection of patients, phase 2 vs phase 3 [trial designs], and so on. Maybe it is also related to the better way to administer amivantamab subcutaneously, which is associated with a lower risk of administration-related reactions and a better dermatologic [adverse] effect profile.

How does the safety profile of amivantamab/lazertinib look in this patient population? How can clinicians best manage any common toxicities while protecting patient quality of life?

We know that PALOMA-2 was also conducted at a time the investigators were well aware of the dermatologic [adverse] effects of amivantamab. The [phase 2 COCOON trial (NCT06120140)] that implemented moisturizing and doxycycline demonstrated that the benefit of this prophylactic regimen for these patients was ongoing....⁴ Finally, we have systematic anticoagulation, which is recommended for the first 4 months of treatment with amivantamab, to reduce the risk of [venous thromboembolism]. Globally, [this is] probably a better way to [treat] the patient.

What are the next steps for research regarding amivantamab/lazertinib or EGFR-mutated NSCLC as a whole?

The next steps for the treatment of these patients are to continue to optimize the administration of amivantamab. We have also seen the PALOMA-2 cohort with subcutaneous amivantamab every 4 weeks, which is even better for the patient pathway. The other thing is that there are multiple new strategies for the treatment of these patients. Beyond first-line [therapy], we have seen recent data with antibody conjugates, especially those targeting TROP2, like datopotamab deruxtecan and sacituzumab govitecan. We have seen data with immunotherapy like ivonescimab, which is a bispecific VEGF/PD-1 antibody. There are also some ongoing trials with the targeting of MET through tyrosine kinase inhibitors [TKIs], such as savolitinib. There is a lot. We don’t know the best treatment sequencing, but in the end, it’s better for the patients to have multiple options.

What do you hope others take away from the results of your research?

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: [the phase 2 SKIPPirr trial (NCT05663866)] 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.⁵

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. Yang JC, Lu S, Hayashi H, et al. Overall survival with amivantamab-lazertinib in EGFR-mutated advanced NSCLC. N Engl J Med. 2025;393(17):1681-1693. doi:10.1056/NEJMoa2503001
3. Leighl NB, Akamatsu H, Lim SM, et al. Subcutaneous versus intravenous amivantamab, both in combination with lazertinib, in refractory epidermal growth factor receptor-mutated non-small cell lung cancer: primary results from the phase III PALOMA-3 study. J Clin Oncol. 2024;42(30):3593-3605. doi:10.1200/JCO.24.01001
4. 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.
5. 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