Dr Chung on the Potential Role for Ficerafusp Alfa Plus Pembrolizumab in the HPV-Negative HNSCC Paradigm

"This patient population needs better treatments. When we combined ficerafusp alfa with pembrolizumab, the ORR was 54%, and greater than 80% of responders [achieved] a reduction in their tumors of 80% [or greater. These data show that the combination] really produces deep as well as durable responses."

Christine Chung, MD, program lead of Head and Neck Oncology; Research Department Chair of Head and Neck-Endocrine Oncology; chair of the Department of Head and Neck-Endocrine Oncology; and program leader of Head and Neck Oncology at Moffitt Cancer Center, discussed the potential role for ficerafusp alfa (BCA101) plus pembrolizumab (Keytruda) in the larger treatment paradigm for human papillomavirus (HPV)–negative recurrent or metastatic head and neck squamous cell carcinoma (HNSCC), particularly those with a PD-L1 combined positive scores (CPS) of at least 1.

At the 2025 ASCO Annual Meeting, interim findings from the phase 1/1b KEYNOTE-E28 trial (NCT04429542) showed a confirmed objective response rate (ORR) of 54% with the combination among 28 patients with HPV-negative, recurrent or metastatic HNSCC and CPS of 1 or greater. The ORR,including both confirmed and unconfirmed responses, was 64%, with a complete response rate of 21%. Notably, 80% of responders experienced at least 80% tumor shrinkage, and the disease control rate reached 89%. These results suggest not only a high frequency of responses but also substantial depth of response, according to Chung.

Chung emphasized that standard first-line therapy for patients in this population with a PD-L1 CPS of 1 or greater currently consists of pembrolizumab monotherapy. However, clinical outcomes remain suboptimal, particularly among patients with HPV-negative disease. For example, in a prior phase 2 trial (NCT03370276) combining cetuximab (Erbitux) and nivolumab (Opdivo) in this subgroup, the median overall survival (OS) was only 10.7 months in patients with a CPS of 20 or higher. In contrast, ficerafusp alfa plus pembrolizumab yielded a median duration of response of 21.7 months and a median OS of 21.3 months in KEYNOTE-E28.

Ficerafusp alfa is a bifunctional fusion protein designed to simultaneously target EGFR and TGF-β signaling while enhancing immune activation through PD-1 blockade, Chung explained. She noted that this dual-targeted approach may account for the improved efficacy, offering both deeper and more durable responses in a patient population that needs more effective therapeutic options.

Given the activity observed in KEYNOTE-E28, Chung suggested that the combination of ficerafusp alfa and pembrolizumab could represent a meaningful advance in the first-line treatment landscape for HPV-negative HNSCC. Additional studies will be needed to validate these findings in larger, randomized cohorts, but the interim data highlight a potential new standard of care for this high-risk patient population, Chung concluded.