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Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer

Bauman, Julie E. and Ohr, James and Gooding, William E. and Ferris, Robert L. and Duvvuri, Umamaheswar and Kim, Seungwon and Johnson, Jonas T. and Soloff, Adam C. and Wallweber, Gerald and Winslow, John and Gaither-Davis, Autumn and Grandis, Jennifer R. and Stabile, Laura P. (2020) Phase I Study of Ficlatuzumab and Cetuximab in Cetuximab-Resistant, Recurrent/Metastatic Head and Neck Cancer. Cancers, 12 (6). p. 1537. ISSN 2072-6694

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etuximab, 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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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Bauman, Julie E.
Ohr, James
Gooding, William E.weg@pitt.eduweg0000-0001-9070-3559
Ferris, Robert L.ferrisrl@upmc.edu0000-0001-6605-2071
Duvvuri, Umamaheswarumd3@pitt.eduumd30000-0003-1968-3756
Kim, Seungwon
Johnson, Jonas T.jonasj@pitt.edujonasj
Soloff, Adam C.AdamSoloff@pitt.eduAdamSoloff
Wallweber, Gerald
Winslow, John
Gaither-Davis, Autumnagaither@pitt.eduagaither
Grandis, Jennifer R.
Stabile, Laura P.stabilela@upmc.edu0000-0002-1822-2707
Date: 11 June 2020
Date Type: Publication
Journal or Publication Title: Cancers
Volume: 12
Number: 6
Publisher: MDPI AG
Page Range: p. 1537
DOI or Unique Handle: 10.3390/cancers12061537
Schools and Programs: School of Medicine > Medicine
Refereed: Yes
Uncontrolled Keywords: HNSCC, cetuximab, ficlatuzumab, EGFR, HGF, cMet
ISSN: 2072-6694
Official URL:
Funders: AVEO Oncology and Biodesix, National Cancer Institute
Article Type: Research Article
Date Deposited: 14 Jun 2021 18:35
Last Modified: 14 Jun 2021 18:35


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