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
Abstract
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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Details
| Item Type: |
Article
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| Status: |
Published |
| Creators/Authors: |
| Creators | Email | Pitt Username | ORCID  |
|---|
| Bauman, Julie E. | | | | | Ohr, James | | | | | Gooding, William E. | weg@pitt.edu | weg | 0000-0001-9070-3559 | | Ferris, Robert L. | ferrisrl@upmc.edu | | 0000-0001-6605-2071 | | Duvvuri, Umamaheswar | umd3@pitt.edu | umd3 | 0000-0003-1968-3756 | | Kim, Seungwon | | | | | Johnson, Jonas T. | jonasj@pitt.edu | jonasj | | | Soloff, Adam C. | AdamSoloff@pitt.edu | AdamSoloff | | | Wallweber, Gerald | | | | | Winslow, John | | | | | Gaither-Davis, Autumn | agaither@pitt.edu | agaither | | | Grandis, Jennifer R. | | | | | Stabile, Laura P. | stabilela@upmc.edu | | 0000-0002-1822-2707 |
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| 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: |
http://dx.doi.org/10.3390/cancers12061537 |
| 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 |
| URI: |
http://d-scholarship.pitt.edu/id/eprint/41292 |
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