The combination of ficlatuzumab and cetuximab has demonstrated antitumor activity in patients with pan-refractory, recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), according to research published in the Journal of Clinical Oncology.

Only patients with HPV-negative HNSCC responded to the combination, and progression-free survival (PFS) was superior in these patients, researchers noted.

The phase 2 trial ( Identifier: NCT03422536) included 58 patients with recurrent or metastatic HNSCC who were randomly assigned to ficlatuzumab monotherapy (n=27) or ficlatuzumab plus cetuximab (n=33). 

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Forty-one percent of patients in the monotherapy arm were HPV-positive, as were 52% of patients in the combination arm. In both arms, nearly all patients had disease that was refractory to platinum therapy, anti-PD-1 therapy, and cetuximab. 

The primary endpoint was PFS, and each treatment arm was compared with historical control individuals. Significance was met for the combination arm, but the monotherapy arm was closed early due to futility.

The median PFS was 3.7 months in patients who received ficlatuzumab plus cetuximab and 1.8 months in those who received ficlatuzumab monotherapy.

In the combination arm, the median PFS differed depending on HPV status. The median PFS was 2.3 months in HPV-positive patients and 4.1 months in HPV-negative patients (P =.03).

The median overall survival was 6.4 months with ficlatuzumab monotherapy and 7.4 months with the combination. 

The objective response rate (ORR) was 4% in the monotherapy arm. The sole responder was a patient with HPV-negative disease, and the response lasted 22 weeks. 

In the combination arm, the ORR was 19%, which included 2 patients who achieved a complete response and 4 with a partial response. The median duration of response was 46 weeks. The ORR was 0% among HPV-positive patients and 38% among HPV-negative patients (P =.02).  

In the monotherapy arm, the most common adverse events (AEs) were hypoalbuminemia (66%) and edema (25%). In the combination arm, the most common AEs were acneiform rash (82%), hypoalbuminemia (76%), and edema (44%). There were 2 treatment-related deaths, 1 in each treatment group.

“[T]he combination of ficlatuzumab and cetuximab prolonged PFS relative to historical control in pan-refractory, recurrent/metastatic HNSCC, whereas ficlatuzumab monotherapy did not,” the researchers wrote. “The association between PFS and HPV status, a biomarker prospectively determined through standard clinical practice, is noteworthy.”

Disclosures: This research was partly supported by Aveo Oncology. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Bauman JE, Saba NF, Roe D, et al. Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, recurrent/metastatic head and neck cancer. J Clin Oncol. Published online March 28, 2023. doi:10.1200/JCO.22.01994