Pyxis Oncology reported updated Phase 1 results for micvotabart pelidotin, or MICVO, in patients with recurrent or metastatic head and neck squamous cell carcinoma receiving second-line treatment or later. Among 33 evaluable patients treated with 5.4 mg/kg intravenously every three weeks, MICVO generated a 36% confirmed objective response rate and a 94% disease control rate. Median progression-free survival was 6.2 months, the 12-month overall survival probability was 79%, and median overall survival had not been reached. Responses were observed across HPV and prior-treatment subgroups, including a 28% response rate among patients previously treated with EGFR inhibitors and 47% among those without such exposure. The antibody-drug conjugate targets extradomain-B of fibronectin in the tumor extracellular matrix. Safety remained a concern, with 54.3% of 35 safety-evaluable patients experiencing Grade 3 or higher treatment-related adverse events and 14.3% discontinuing treatment, although no treatment-related deaths or new safety signals were reported. A dose cap reduced adverse-event severity in heavier patients. Shares fell 7% Tuesday as William Blair analyst Andy Hsieh described tolerability as a key liability. Pyxis plans to meet with the FDA in the first quarter of 2027 through Project Optimus to finalize dosing before a planned 500-patient, open-label Phase 3 trial, named Headliner, in mid-2027. The study will compare MICVO with investigator's choice of cetuximab, docetaxel or methotrexate. Additional Phase 1/2 data on MICVO combined with Merck's KEYTRUDA are expected in the fourth quarter of 2026, with combination durability metrics and a recommended Phase 3 dose expected by late 2027.