Related Experiment Video
Updated: Aug 5, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Randomized Phase II Trial of Ficlatuzumab With or Without Cetuximab in Pan-Refractory, Recurrent/Metastatic Head and
Julie E Bauman1,2, Nabil F Saba3, Denise Roe4,5
1Division of Hematology/Oncology, Department of Medicine, George Washington (GW) University and GW Cancer Center, Washington, DC.
Purpose:
Primary or acquired resistance to cetuximab, an antiepidermal growth factor receptor monoclonal antibody (mAb), minimizes its utility in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC). Aberrant hepatocyte growth factor/cMet pathway activation is an established resistance mechanism. Dual pathway targeting may overcome resistance.
Patients And Methods:
This multicenter, randomized, noncomparative phase II study evaluated ficlatuzumab, an antihepatocyte growth factor mAb, with or without cetuximab in recurrent/metastatic HNSCC. The primary end point was median progression-free survival (PFS); an arm met significance criteria if the lower bound of the 90% CI excluded the historical control of 2 months. Key eligibility criteria were HNSCC with known human papillomavirus (HPV) status, cetuximab resistance (progression within 6 months of exposure in the definitive or recurrent/metastatic setting), and resistance to platinum and anti-PD-1 mAb. Secondary end points included objective response rate (ORR), toxicity, and the association of HPV status and cMet overexpression with efficacy. Continuous Bayesian futility monitoring was used.
Results:
From 2018 to 2020, 60 patients were randomly assigned and 58 were treated. Twenty-seven versus 33 patients were allocated to monotherapy versus combination. Arms were balanced for major prognostic factors. The monotherapy arm closed early for futility. The combination arm met prespecified significance criteria with a median PFS of 3.7 months (lower bound 90% CI, 2.3 months; P = .04); the ORR was 6 of 32 (19%), including two complete and four partial responses. Exploratory analyses were limited to the combination arm: the median PFS was 2.3 versus 4.1 months (P = .03) and the ORR was 0 of 16 (0%) versus 6 of 16 (38%; P = .02) in the HPV-positive versus HPV-negative subgroups, respectively. cMet overexpression was associated with reduced hazard of progression in HPV-negative but not HPV-positive disease (P interaction = .02).
Conclusion:
The ficlatuzumab-cetuximab arm met significance criteria for PFS and warrants phase III development. HPV-negative HNSCC merits consideration as a selection criterion.
Insights
Dual targeting with ficlatuzumab and cetuximab shows promise for recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) resistant to prior therapies. The combination therapy met PFS significance criteria, suggesting potential for HPV-negative HNSCC patient selection.
Area of Science:
- Oncology
- Immunotherapy
- Molecular Targeted Therapy
Background:
- Resistance to cetuximab (anti-EGFR mAb) limits its efficacy in recurrent/metastatic head and neck squamous cell carcinoma (HNSCC).
- Hepatocyte growth factor (HGF)/cMet pathway activation is a known mechanism of cetuximab resistance.
- Dual pathway inhibition may overcome acquired resistance in HNSCC.
Purpose of the Study:
- To evaluate ficlatuzumab (anti-HGF mAb) combined with cetuximab in patients with recurrent/metastatic HNSCC who are resistant to prior therapies.
- To assess the primary endpoint of median progression-free survival (PFS) for the combination therapy.
- To explore the association of HPV status and cMet overexpression with treatment efficacy.
Main Methods:
- A multicenter, randomized, noncomparative phase II study enrolled 60 patients with HNSCC resistant to platinum, anti-PD-1 mAb, and cetuximab.
- Patients received either ficlatuzumab monotherapy or ficlatuzumab plus cetuximab.
- Primary endpoint: median PFS; secondary endpoints: objective response rate (ORR), toxicity, and biomarker associations. Futility monitoring was employed.
Main Results:
- The ficlatuzumab-cetuximab arm met prespecified significance criteria for PFS (median 3.7 months; 90% CI, 2.3 months; P = .04).
- The objective response rate (ORR) in the combination arm was 19% (6/32), including complete and partial responses.
- In exploratory analyses, HPV-negative HNSCC patients showed significantly improved PFS (4.1 vs 2.3 months) and ORR (38% vs 0%) compared to HPV-positive patients.
Conclusions:
- The combination of ficlatuzumab and cetuximab demonstrated significant PFS and warrants further investigation in Phase III trials.
- The study suggests that HPV-negative HNSCC may be a predictive biomarker for selecting patients for this combination therapy.
- Targeting both EGFR and HGF/cMet pathways offers a potential strategy to overcome resistance in HNSCC.
More Related Videos
04:04Endobronchial Ultrasound-guided Intratumoral Injection of Cisplatin for the Treatment of Isolated Mediastinal Recurrence of Lung Cancer
Published on: February 12, 2017
06:15Tumor Treating Field Therapy in Combination with Bevacizumab for the Treatment of Recurrent Glioblastoma
Published on: October 27, 2014
