SC Amivantamab Achieves Strong Response Rate in HNSCC

Subcutaneous amivantamab (Rybrevant Faspro) demonstrated high response rates with durable remissions in patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) who had previously received immune checkpoint inhibitor (ICI) and platinum-based chemotherapy, according to results from the phase 1b/2 OrigAMI-4 study (NCT06385080) presented at the 2026 ASCO Annual Meeting and simultaneously published in the Journal of Clinical Oncology.^1,2

Among 102 patients treated with subcutaneous amivantamab every 3 weeks, best responses included complete response (CR) in 15% and partial response in 27% of patients, yielding a confirmed objective response rate (ORR) of 42% by blinded independent central review (BICR) and a clinical benefit rate of 63% (95% CI, 53-72). Median time to first response was rapid at 6.6 weeks (range, 5.6-36.9). Investigator-assessed ORR was 47% (95% CI, 37-57), consistent with BICR results. Among patients with at least 1 post-baseline disease assessment, 84% experienced tumor shrinkage of target lesions.

Among the 43 confirmed responders, median duration of response (DOR) was not reached (95% CI, 6.9-NR) at a median follow-up of 11.8 months (range, 1.1-21.9). Fifty-six percent of responders had a response duration of 6 months or greater, 63% of responses were ongoing at data cutoff, and 13 of 15 CRs (87%) remained ongoing.

The ORR of 42% was consistent across all prespecified subgroups, including age, sex, race, ECOG performance status (PS), smoking history, and number of prior lines of therapy. A notably higher ORR was observed in patients with oral cavity primary tumors (56%; n = 27/48) compared with non-oral cavity primaries (30%; n = 16/54).

At a median follow-up of 11.8 months, median progression-free survival (PFS) was 6.8 months (95% CI, 5.2-8.3), with 53% of patients progression-free at 6 months and 23% at 12 months (95% CI, 13-35). Median overall survival (OS) was 12.5 months (95% CI, 10.2-16.8), with 78% of patients alive at 6 months and 54% alive at 1 year (95% CI, 42-64).

"Patients with recurrent or metastatic head and neck cancer who have already been treated with immunotherapy and chemotherapy face very poor outcomes," Barbara Burtness, MD, medical oncologist and professor of medicine at Yale Cancer Center in New Haven, Connecticut, stated in a news release. ² "The high response seen with subcutaneous amivantamab on its own, including more than one-third of responders achieving complete responses, and the durability of those responses, suggests it has the potential to meaningfully improve expectations for these patients."

Amivantamab Safety in HNSCC

The safety profile of subcutaneous amivantamab was consistent with prior reports of the subcutaneous formulation, with adverse events (AEs) largely reflecting on-target EGFR and MET inhibition and mostly grade 1 or 2 in severity. Median treatment duration was 5.9 months (range, 0.0-18.9).

The most common treatment-emergent AEs occurring in 20% or more of patients included hypoalbuminemia (any grade, 50%; grade 3 or higher, 5%), rash (37%; 3%), acneiform dermatitis (34%; 6%), paronychia (34%; 2%), stomatitis (28%; 2%), fatigue (28%; 4%), hypocalcemia (25%; 1%), peripheral edema (24%; 1%), and anemia (22%; 5%). Administration-related reactions were reported in 15% of patients (grade 1, 9%; grade 2, 6%). Treatment-related discontinuations occurred in 8% of patients. One patient had a treatment-related pneumonitis resulting in death; five additional deaths due to AEs were deemed unrelated to amivantamab. No new safety signals were identified.

OrigAMI-4 Study Design and HNSCC Patient Characteristics

OrigAMI-4 is a phase 1b/2, open-label, multicenter study evaluating subcutaneous amivantamab across multiple cohorts in patients with R/M HNSCC. Cohort 1, the focus of this presentation, enrolled patients with R/M HNSCC who had received prior ICI and platinum-based chemotherapy, had no prior anti-EGFR therapy, and had an ECOG PS of 0 or 1. Patients with p16-positive oropharyngeal carcinoma were excluded. Subcutaneous amivantamab was administered at 2400 mg (or 3360 mg if body weight was 80 kg or greater) every 3 weeks.

A total of 102 patients were enrolled. Median age was 63 years (range, 30-81), and 77% were male. By race, 44% were Asian, 41% were White, and 15% were other. ECOG PS was 0 in 33% and 1 in 67% of patients. Primary tumor locations included oral cavity (47%), larynx (24%), hypopharynx (16%), and oropharynx (14%). With respect to location of R/M disease at screening, 49% had locoregional and distant disease, 30% had locoregional only, and 21% had distant only. All 102 patients had received prior systemic therapy in the R/M setting, with 52% having received 1 prior line and 48% having received 2 prior lines. Amivantamab treatment was ongoing in 31% of patients (n = 32/102) at data cutoff.

The rationale for dual EGFR-MET targeting in HNSCC is supported by the overexpression of both receptors in 80%-90% of HPV-independent tumors.

References

1. Burtness B, Harrington KJ, Ji D, et al. Amivantamab in recurrent/metastatic head and neck squamous cell carcinoma after immune checkpoint inhibitor and chemotherapy: pivotal results from the phase 1b/2 OrigAMI-4 study. J Clin Oncol. 2026. doi:10.1200/JCO-26-01042

2. Johnson & Johnson. RYBREVANT FASPRO (amivantamab and hyaluronidase-lpuj) pivotal data show strong and durable responses in advanced head and neck cancer where options remain limited. News release. May 31, 2026. Accessed June 19, 2026. https://www.prnewswire.com/news-releases/rybrevant-faspro-amivantamab-and-hyaluronidase-lpuj-pivotal-data-show-strong-and-durable-responses-in-advanced-head-and-neck-cancer-where-options-remain-limited-302786430.html