FDA Grants Fast Track Designation to Ficlatuzumab for Relapsed or Recurrent HNSCC

Michael Bailey

The FDA has granted a fast track designation to ficlatuzumab (formerly AV-299) for the treatment of patients with relapsed or recurrent head and neck squamous cell carcinoma (HNSCC).¹

Previously reported findings from a phase 2 trial (NCT03422536) showed that the combination of ficlatuzumab and cetuximab (Erbitux) elicited a median progression-free survival (PFS) of 3.6 months in patients with recurrent/metastatic HNSCC.² Single-agent ficlatuzumab produced a median PFS of 1.8 months

“The FDA’s decision to grant fast track designation underscores the potential for ficlatuzumab to address a serious unmet need and serve as a meaningful therapeutic option for patients with metastatic HNSCC,” Michael Bailey, president and chief executive officer of AVEO, stated in a press release. “We are committed to unlocking the full potential of ficlatuzumab in patients with HNSCC and look forward to working closely with the FDA to determine next steps for the program.”

Ficlatuzumab is an investigational HGF IgG1 inhibitory antibody that binds to the HGF ligand with high affinity and specificity. The agent is under investigation in HNSCC and metastatic pancreatic ductal cancer.

The phase 2 trial investigated ficlatuzumab monotherapy and in combination with cetuximab in patients with histologically confirmed recurrent/metastatic HNSCC from any primary site, except nasopharyngeal if WHO Type III (non-keratinizing and EBV-positive).³

Patients were required to be resistant or ineligible for platinum-based chemotherapy and be resistant to cetuximab with progression on or within 6 months of exposure in the definitive or recurrent/metastatic setting. They also needed to have prior treatment with or be ineligible for an anti–PD-1 monoclonal antibody. An ECOG performance status of 0 or 1 and no significant medical comorbidities were also required.

Enrolled patients were randomly assigned to receive 20 mg/kg of intravenous ficlatuzumab every 2 weeks, with or without 500 mg/m² of cetuximab every 2 weeks.

The primary end point of the trial was PFS, and secondary end points included overall response rate (ORR), overall survival, biomarker analysis, quality of life, and safety.

Additional data in the combination arm showed patients experienced an ORR of 19%, with 2 patients achieving a complete response and 4 patients having a partial response (PR). In the ficlatuzumab monotherapy arm, the ORR was 4%, with 1 patient experiencing a PR. Notably, all responses in both arms were observed in HPV-negative patients.

Regarding safety, grade 1/2 adverse effects (AEs) reported in more than 10% of patients in the ficlatuzumab monotherapy arm included hypoalbuminemia (30%) and peripheral edema (15%). Grade 3 or higher AEs included pneumonitis (8%), facial/HN edema (4%), and maculopapular rash (4%).

In the combination arm, grade 1/2 AEs reported in more than 10% of patients included acneiform rash (44%), hypoalbuminemia (31%), and peripheral edema (16%). Grade 3 or higher AEs included acneiform rash (19%), peripheral edema (3%), cardiopulmonary arrest (3%), fatigue (3%), paronychia (3%), diarrhea (3%), and elevated AST/ALT (3%).

References

1. AVEO Oncology announces ficlatuzumab granted fast track designation by the U.S. FDA for the treatment of relapsed or recurrent head and neck squamous cell carcinoma. News release. AVEO Oncology. September 20, 2022. Accessed September 23, 2022. https://bit.ly/3BMxWs2
2. Bauman JE, Saba NF, Roe D, et al. Randomized phase II trial of ficlatuzumab with or without cetuximab in pan-refractory, advanced head and neck squamous cell carcinoma (HNSCC). J Clin Oncol. 2021;39(suppl 15):6015. doi:10.1200/JCO.2021.39.15_suppl.6015
3. Ficlatuzumab w/wo cetuximab in patients w/cetuximab-resistant, recurrent or metastatic head/neck squamous cell carcinoma. ClinicalTrials.gov. Updated September 13, 2022. Accessed September 23, 2022. https://clinicaltrials.gov/ct2/show/NCT03422536