Subcutaneous amivantamab produced a 42% objective response rate and a 15% complete response rate in patients with recurrent/metastatic HNSCC.
Subcutaneous amivantamab and hyaluronidase-lpuj (Rybrevant Faspro) monotherapy produced a confirmed objective response rate (ORR) of 42% (95% CI, 32%-52%) by blinded independent central review (BICR), including a complete response (CR) rate of 15%, in patients with recurrent or metastatic (R/M), HPV-unrelated head and neck squamous cell carcinoma (HNSCC) whose disease had progressed after an immune checkpoint inhibitor (ICI) and platinum-based chemotherapy, according to data from cohort 1 of the phase 1b/2 OrigAMI-4 study (NCT06385080) presented during the
Investigator-assessed ORR was consistent with the BICR results at 47% (95% CI, 37%-57%), and among participants with at least 1 postbaseline disease assessment, 84% experienced tumor shrinkage of target lesions. Among the 43 confirmed responders, median time to first response was 6.6 weeks (range, 5.6-36.9). The clinical benefit rate was 63% (95% CI, 53%-72%).
In July 2026, the FDA granted priority review to the supplemental biologics license application (sBLA) for subcutaneous amivantamab and hyaluronidase in adults with R/M HNSCC whose disease has progressed following platinum-based chemotherapy and a PD-1 or PD-L1 inhibitor.2 The sBLA was supported by data from OrigAMI-4.
OrigAMI-4 was an open-label, multicohort phase 1b/2 study; cohort 1 enrolled 102 participants with R/M HNSCC who had not received prior anti-EGFR therapy and who had documented progression on or after a PD-(L)1 inhibitor and platinum-based chemotherapy, given either in combination or as separate lines of therapy.¹ Patients with p16-positive oropharyngeal carcinoma were excluded, and ECOG performance status was required to be 0 or 1.
Subcutaneous amivantamab was administered at 2400 mg (3360 mg for patients weighing ≥80 kg) every 3 weeks.
The primary end point was ORR by RECIST v1.1, confirmed via BICR; secondary end points included duration of response, clinical benefit rate, progression-free survival (PFS), OS, and safety.
Median patient age was 63 years (range, 30-81), and 77% of participants were male. Primary tumor sites included the oral cavity (47%), larynx (24%), hypopharynx (16%), and oropharynx (14%). All participants had received both an ICI and platinum-based chemotherapy in prior lines, with 52% having received 1 prior line and 48% having received 2 prior lines of systemic therapy.
ORR was generally consistent across prespecified subgroups, including by age, sex, ECOG performance status, race, and number of prior therapy lines. Response rates were numerically higher among participants with oral cavity primary tumors (56%; 95% CI, 41%-71%) than among those with non–oral cavity primaries (30%; 95% CI, 18%-44%).
At a median follow-up of 11.8 months (range, 1.1-21.9), median duration of response was not reached (95% CI, 6.9 months-NR) among the 43 confirmed responders, and 63% of responses were ongoing at data cutoff; among the 15 patients with a CR, 13 (87%) remained in response. Median PFS was 6.8 months (95% CI, 5.2-8.3), with 53% of participants progression-free at 6 months and 23% at 12 months. Median OS was 12.5 months (95% CI, 10.2-16.8), with 78% of participants alive at 6 months and 54% alive at 1 year.
Median treatment duration was 5.9 months. Adverse effects (AEs) were largely attributable to on-target EGFR or MET inhibition and were mostly grade 1 or 2. The most common treatment-emergent AEs of any grade included hypoalbuminemia (50%), rash (37%), acneiform dermatitis (34%), paronychia (34%), fatigue (28%), stomatitis (28%), hypocalcemia (25%), peripheral edema (24%), and anemia (22%); grade 3 or higher events occurred in no more than 6% of patients for any individual preferred term. Administration-related reactions specific to the subcutaneous formulation were reported in 15% of participants (grade 1, 9%; grade 2, 6%). Treatment-related discontinuations occurred in 8% of patients. One participant had treatment-related pneumonitis resulting in death; 5 additional deaths from AEs were reported and were deemed unrelated to amivantamab. Investigators reported no new safety signals, with a profile consistent with prior reports of subcutaneous amivantamab.
Investigators are now evaluating subcutaneous amivantamab plus pembrolizumab (Keytruda) and carboplatin against a 5-fluorouracil–based regimen with pembrolizumab and platinum chemotherapy as first-line treatment for R/M HNSCC, irrespective of PD-L1 status, in the ongoing phase 3 OrigAMI-5 study (NCT07276399).
