SC Amivantamab May Provide More Convenience in CHRYSALIS-2 Regimen

In cohort C of the phase 1/1b CHRYSALIS-2 trial (NCT04077463), combining first-line amivantamab-vmjw (Rybrevant) with lazertinib (Lazcluze) improved overall survival (OS) among patients with atypical EGFR-mutated non–small cell lung cancer (NSCLC).¹ Although amivantamab was administered intravenously in this trial, switching to the subcutaneous formulation of amivantamab (Rybrevant Faspro) may provide additional benefits and convenience for patients, according to Joel W. Neal, MD, PhD.

At the 2026 American Society of Clinical Oncology Annual Meeting (ASCO), Neal discussed how subcutaneous amivantamab may be the “preferred form” of the agent when administering the CHRYSALIS-2 regimen to patients. Although subcutaneous therapy may show unique challenges regarding cutaneous toxicity, it could nevertheless avoid infusion-related reactions and time toxicities associated with intravenous amivantamab.

Neal is a professor of medicine (Oncology) at Stanford Cancer Institute in Palo Alto, California.

Transcript:

It’s interesting to note that in CHRYSALIS-2, the intravenous form of amivantamab was used, [with] the dosing of [intravenous therapy] every week for 4 weeks, and then every 2 weeks ongoing. In addition, this study was conducted before the supportive care regimen from the COCOON study [NCT06120140] to help prevent dermatologic adverse events, and the SKIPPirr study [NCT05663866] to prevent infusion-related reactions were employed.^2,3 The infusion-related reactions have been [largely] ameliorated by the availability of subcutaneous amivantamab, which came out late last year and is increasingly being utilized by multiple institutions.

In classical EGFR-mutant lung cancer, where we use amivantamab and lazertinib in the frontline setting, most people have switched over to using the subcutaneous formulation instead of the [intravenous] formulation. In addition, some patients who are on the [intravenous] formulation are being converted over to the subcutaneous formulation, too. This is based on data from the PALOMA studies. The subcutaneous formulation looks like it’s going to be the preferred form, and it’ll make it easier for patients to have fewer infusion-related reactions, which is a problem usually on only the first day or 2 of therapy. But it also [offers] convenience. Subcutaneous [treatment] takes 5 minutes per administration, whereas the intravenous [treatment] was taking 5, 6, 7, or 8 hours [for] 2 days in a row, then every single week getting a little shorter over time. It clearly helps improve the time toxicity of patients being able to spend more time away from our oncology centers, which is always a good thing. [It] also seems to avoid some of those early toxicities, although, notably, the cutaneous toxicity and some of the MET-related toxicities like edema look very similar and have to be treated in other ways.

References

1. Neal JW, Yang JCH, Cho BC, et al. Overall survival of first-line amivantamab plus lazertinib in atypical EGFR-mutated advanced non-small cell lung cancer (NSCLC): updated results from the CHRYSALIS-2 study. J Clin Oncol. 2026;44(suppl 16):8501. doi:10.1200/JCO.2026.44.16_suppl.8501
2. 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
3. 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