FIERCE-HN: A multicenter, randomized, double-blind, placebo-controlled, phase 3 study of ficlatuzumab (HGF/cMET MAb) in combination with cetuximab in participants with recurrent or metastatic (R/M) HPV negative head and neck squamous cell carcinoma (HNSCC).
Background: Patients with HPV-negative R/M HNSCC have a worse median overall survival (OS) than HPV-positive patients and current treatments options are limited.[1] Ficlatuzumab is a humanized IgG1 MAb that binds HGF, the ligand for the c-MET tyrosine kinase receptor. HGF/c-MET pathway dysregulation is frequently observed in HPV-negative HNSCC, and has been linked to EGFR inhibitor resistance, limiting the potential efficacy of EGFR-targeting drugs like cetuximab. In a phase 2 study, both pathways were targeted using ficlatuzumab plus cetuximab in patients with HPV-negative R/M HNSCC resistant to cetuximab, platinum, and anti-PD1 immune checkpoint inhibitors (ICI) who have a very poor historical prognosis. A PFS of 4.1 months, median OS of 7.4 months, and overall response rate (ORR) of 38% (6/16; 2 CR, 4 PR) was observed.[2] FIERCE-HN compares the efficacy/safety of ficlatuzumab+cetuximab vs placebo+cetuximab in patients with R/M HPV-negative HNSCC. Methods: This is an international, multicenter, randomized, double-blind, placebo-controlled phase 3 study. Major enrollment criteria include confirmed diagnosis of R/M HNSCC primary tumors of the oropharynx (p-16 negative only), oral cavity, hypopharynx, or larynx. Participants must have progressed on, or be intolerant to, previous anti-PD-1/PD-L1 ICI and platinum-based chemotherapy; have 2 or fewer prior lines of anticancer therapy; and have no prior treatment with cetuximab/alternative EGFR inhibitors in the R/M setting. Patients with feeding tubes are eligible. The primary endpoint is OS; key secondary endpoints include PFS and ORR. Other secondary endpoints are DCR, DoR, safety, PK, immunogenicity and QoL. Patients will receive cetuximab 500mg/m2 and are randomized 1:1:1 to Arm A: ficlatuzumab 10mg/kg, Arm B: ficlatuzumab 20mg/kg, or Arm C: placebo. Treatments will be on Days 1 and 15 of a 28-day cycle. This is an adaptive study with two interim analyses (IAs). IA 1 will be conducted after 70 OS events, when futility and optimal dose assessments will be performed. Participants enrolled after IA 1 will be randomized 1:1 to the optimal ficlatuzumab dose or placebo, plus cetuximab. IA 2 will be conducted after 163 OS events to assess whether an event count re-estimation is needed. The final analysis will occur after 232 (or up to 279) OS events, depending on the re-estimation outcome. The study has statistical power of 80%, assuming a true OS hazard ratio of 0.667. Between 410 to 500 patients will be enrolled. The study is ongoing and actively recruiting in North America, Europe, United Kingdom, and Asia-Pacific. Clinical trial information: NCT06064877 (collaborator Eli Lilly provided cetuximab). 1. Cohen E et al., JITC. 2019;7:184. 2. Bauman JE et al., JCO. 2023. 41:3851.
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Author Details
Julie Bauman
GW Cancer Center, George Washington University, Washington, DC
Abstract Details
Meeting
2025 ASCO Annual Meeting
Session Type
Poster Session
Session Title
Head and Neck Cancer
Track
Head and Neck Cancer
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