Dr Mehra on the Safety Profile of Subcutaneous Amivantamab in HNSCC

“The administration of [subcutaneous] amivantamab…resulted in fewer infusion- or administration-related reactions than what had historically been seen with the intravenous administration.”

Ranee Mehra, MD, director of Head and Neck Medical Oncology and a professor of medicine at the Marlene and Stewart Greenebaum Comprehensive Cancer Center at the University of Maryland Medical System, discussed safety findings with amivantamab and hyaluronidase-lpuj (Rybrevant Faspro; subcutaneous amivantamab) in patients with head and neck squamous cell carcinoma (HNSCC), as seen in the phase 1/2 OrigAMI-4 trial (NCT06385080).

Mehra explained that the adverse effects (AEs) identified during the clinical evaluation of the agent in this population were largely consistent with the expected effects of a bispecific antibody targeting the EGFR and MET pathways. She noted the presence of skin toxicities, such as acneiform rash, which is recognized as a standard class effect of EGFR inhibition. Other reported AEs included hypomagnesemia and low rates of peripheral edema, although Mehra emphasized that these toxicities were predominantly categorized as grade 1 or 2, aligning with the known mechanism of action of intravenous (IV) amivantamab-vmjw (Rybrevant).

Mehra highlighted a significant clinical advantage regarding the delivery method of the treatment. She stated that the subcutaneous administration of amivantamab resulted in a lower frequency of administration-related reactions compared with the historical benchmarks established by IV delivery of the drug.

Specifically, in cohort 1 of the trial, which investigated subcutaneous amivantamab monotherapy in patients with human papillomavirus–unrelated recurrent or metastatic HNSCC who had previously received a PD-(L)1 inhibitor and platinum-based chemotherapy, the most common grade 3 or higher treatment-emergent AEs included dermatitis acneiform (7%), anemia (6%), fatigue (5%), lymphopenia (5%), increased alanine aminotransferase levels (3%), rash (2%), pruritus (2%), hypoalbuminemia (2%), dyspnea (2%), and increased aspartate aminotransferase levels (2%). Furthermore, the rate of administration-related reactions was 7%, and all cases were grade 1/2.