3609 - FIERCE-HN: A Multicenter, Randomized, Placebo-Controlled, Phase 3 Study of Ficlatuzumab + Cetuximab in Pts W/ Recurrent or Metastatic (R/M) HPV-Negative Head and Neck Squamous Cell Carcinoma (HNSCC)

J. E. Bauman¹, K. Allman², and R. I. Haddad³; ¹Medical Oncology, George Washington University School of Medicine and Health Sciences, Washington, DC, ²AVEO Oncology, Boston, MA, ³Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA

Purpose/Objective(s): For patients with R/M HNSCC, current treatments are palliative with anti-PD-1 checkpoint inhibitor +/- platinum and 5-fluorouracil chemotherapy for first-line followed by taxanes, methotrexate, and cetuximab as later-line options. The median overall survival (OS) for R/M patients is 10-13 months, and those with HPV-negative HNSCC face the worst outcomes.[1] Ficlatuzumab is a humanized IgG1 mAB against HGF, the ligand for the c-MET tyrosine kinase receptor. HGF/c-MET pathway dysregulation is frequently observed in HPV-negative HNSCC. In a phase 2 study, ficlatuzumab 20mg/kg plus cetuximab 500mg/m² every 2 weeks was assessed in R/M HNSCC patients that were anti-PD-1, cetuximab, and platinum-resistant, a pan-refractory population with a median PFS of 2 months[2]. In this study, HPV-negative patients had a progression-free survival (PFS) of 4.1 months, median OS of 7.4 months, and overall response rate (ORR) of 38% (6/16; 2 CR, 4 PR)[2]. The objective of the FIERCE-HN study is to compare the efficacy/safety of ficlatuzumab+cetuximab vs placebo+cetuximab in patients with R/M HPV-negative HNSCC. Materials/

Methods: FIERCE-HN is an international, multicenter, randomized, double-blind, placebo-controlled phase 3 study. Major enrollment criteria include confirmed primary diagnosis of HPV-negative R/M HSNCC; primary tumor of oropharynx, oral cavity, hypopharynx, or larynx; failed or intolerant to previous anti-PD-1/PD-L1 and platinum chemotherapy; no more than 2 prior lines of anticancer therapy; no prior treatment with cetuxiumab/alternative EGFR inhibitors in the R/M setting. Patients with feeding tubes are eligible. Approximately 410 patients will be randomized 1:1:1 to Arm A: ficlatuzumab 10mg/kg plus cetuximab 500mg/m², Arm B: ficlatuzumab 20mg/kg plus cetuximab 500mg/m², or Arm C: placebo plus cetuximab 500mg/m². Treatments will be on Days 1 and 15 of a 28-day cycle. An interim analysis will be done to determine optimal dose of ficlatuzumab for further study progression when 70 patients each in Arms A and B have completed their first restaging scans (the inferior ficlatuzumab arm will be discontinued; final target n of ~163 in each the optimal ficlatuzumab and control arms). The primary endpoint is OS; additional endpoints include PFS, ORR, DCR, DoR, safety, PK/PD, QoL, and antidrug antibodies. A total of 239 events are required to have 87.5% power to detect a difference assuming a true HR=0.67 in favor of the optimal ficlatuzumab+cetuximab arm after the interim analysis. Analysis will use a 1-sided log-rank test at a significance level= 0.025 and the uniformly most powerful conditionally unbiased criterion to control the Type 1 error.

1. Cohen E et al. J. Immunotherapy Cancer. 2019;7:184.
2. Bauman JE et al. J Clin Oncol. 2023 Mar 28;JCO2201994.

Results: TBD
Conclusion: TBD