Phase i study of ficlatuzumab and cetuximab in cetuximab-resistant, recurrent/metastatic head and neck cancer

Julie E. Bauman, James Ohr, William E. Gooding, Robert L. Ferris, Umamaheswar Duvvuri, Seungwon Kim, Jonas T. Johnson, Adam C. Soloff, Gerald Wallweber, John Winslow, Autumn Gaither-Davis, Jennifer R. Grandis, Laura P. Stabile

Research output: Contribution to journalArticlepeer-review

15 Scopus citations


Cetuximab, an anti-EGFR monoclonal antibody (mAb), is approved for advanced head and neck squamous cell carcinoma (HNSCC) but benefits a minority. An established tumor-intrinsic resistance mechanism is cross-talk between the EGFR and hepatocyte growth factor (HGF)/cMet pathways. Dual pathway inhibition may overcome cetuximab resistance. This Phase I study evaluated the combination of cetuximab and ficlatuzumab, an anti-HGF mAb, in patients with recurrent/metastatic HNSCC. The primary objective was to establish the recommended Phase II dose (RP2D). Secondary objectives included overall response rate (ORR), progression-free survival (PFS), and overall survival (OS). Mechanistic tumor-intrinsic and immune biomarkers were explored. Thirteen patients enrolled with no dose-limiting toxicities observed at any dose tier. Three evaluable patients were treated at Tier 1 and nine at Tier 2, which was determined to be the RP2D (cetuximab 500 mg/m2 and ficlatuzumab 20 mg/kg every 2 weeks). Median PFS and OS were 5.4 (90% CI = 1.9–11.4) and 8.9 (90% CI = 2.7–15.2) months, respectively, with a confirmed ORR of 2 of 12 (17%; 90% CI = 6–40%). High circulating soluble cMet levels correlated with poor survival. An increase in peripheral T cells, particularly the CD8+ subset, was associated with treatment response whereas progression was associated with expansion of a distinct myeloid population. This well-tolerated combination demonstrated promising activity in cetuximab-resistant, advanced HNSCC.

Original languageEnglish (US)
Article number1537
Pages (from-to)1-17
Number of pages17
Issue number6
StatePublished - Jun 2020


  • CMet
  • Cetuximab
  • EGFR
  • Ficlatuzumab
  • HGF

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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