Dr Muzaffar on the Evaluation of FLX475 Plus Pembrolizumab in HNSCC

Jameel Muzaffar, MD, instructor, Department of Medicine, Medical Oncology, Duke Cancer Institute, discusses findings from and future implications of the phase 1/2 FLX475-02 trial (NCT03674567) investigating the CCR4 antagonist FLX475 (tivumecirnon) plus pembrolizumab (Keytruda) in patients with head and neck squamous cell carcinoma (HNSCC), particularly those previously treated with checkpoint inhibitor.

In a study involving approximately 32 patients with metastatic HNSCC who had undergone multiple lines of therapy, all of whom had previously received checkpoint inhibitors, a combination treatment was administered comprising FLX475, an oral medication taken daily, along with pembrolizumab given every 3 weeks, Muzaffar begins. The study's findings were stratified based on patients’ HPV status and PD-L1 combined positive score scores, he adds. Notably, an overall response rate of approximately 16% was observed in this patient cohort, a significant result given their resistance to checkpoint inhibitor therapy, he reports.

Interestingly, within this study, a higher response rate of approximately 20% was noted among patients who tested positive for HPV, Muzaffar explains. Moreover, some of these patients experienced durable responses lasting up to 2 years, with ongoing follow-up for others still ongoing. Despite concerns about treatment toxicity, particularly QTc prolongation, dose adjustments effectively managed this issue, enabling most patients to complete the treatment regimen with minimal adverse effects and high tolerability, he elucidates.

This study, though small in scale, has shown promising signals warranting further investigation, Muzaffar continues. Future plans involve analyzing survival data, exploring the tumor microenvironment, and investigating the pathology of responders to guide the design of subsequent studies. There is potential for a larger phase 3 trial, possibly focusing on the HPV-positive patient population, which is growing due to decreasing smoking rates over recent decades, he notes. The combination therapy used in this study may hold promise for effectively treating this specific patient group, Muzaffar concludes.