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Ref Type Journal Article
PMID (32545260)
Authors Bauman JE, Ohr J, Gooding WE, Ferris RL, Duvvuri U, Kim S, Johnson JT, Soloff AC, Wallweber G, Winslow J, Gaither-Davis A, Grandis JR, Stabile LP
Title Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer.
Journal Vol Issue Date Pages Journal Short Title
Cancers 12 6 2020 Jun 11 Cancers (Basel)
URL
Abstract Text 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.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Ficlatuzumab Ficlatuzumab 0 2
Drug Name Trade Name Synonyms Drug Classes Drug Description
Ficlatuzumab AV-299|SCH900105 HGF Antibody 4 Ficlatuzumab (AV-299) is a monoclonal antibody that targets HGF and inhibits c-MET/HGF signaling, potentially resulting in decreased tumor growth (PMID: 23493885, PMID: 29346833, PMID: 32545260).
Gene Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References