Enhanced Efficacy of sEphB4-HSA + Pembro in HPV-Negative HNSCC

July, 07, 2024 | Head & Neck Cancer


  • The study aimed to evaluate safety, efficacy, and HPV/EphrinB2 impact of sEphB4-HSA + pembro in patients with advanced HNSCC.
  • The primary endpoints were safety and tolerability.
  • The combination of sEphB4-HSA and pembro demonstrated a favorable toxicity profile and activity.

Patients experiencing relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) following primary local therapy exhibit limited response rates to cetuximab, systemic chemotherapy, or checkpoint inhibitor therapy. The pursuit of novel combination therapies to enhance HNSCC outcomes remains a critical area of unmet need.

Alexandra Jackovich and the team aimed to evaluate the safety, tolerability, and overall response rate (ORR) of EphB4-human serum albumin (sEphB4-HSA) and pembrolizumab (pembro) in patients with relapsed or metastatic HNSCC.

This phase II single-arm clinical trial evaluated patients with locally advanced or metastatic HNSCC treated with a combination of soluble sEphB4-HSA fusion protein and pembro following up to 2 prior lines of platinum-based chemotherapy.

The primary endpoints were safety and tolerability, with ORR as the primary efficacy endpoint. Secondary endpoints included progression-free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were assessed for their impact on outcomes.

About 25 patients were enrolled with a median follow-up of 40.4 months (range 9.8 – 40.4). There were 6 responders, resulting in an ORR of 24%. Among the 11 HPV-negative and EphrinB2-positive patients, there were 5 responders, yielding an ORR of 45%, with 2 of these patients achieving a complete response (CR).

The median PFS in HPV-negative/EphrinB2-positive patients was 3.2 months (95% CI [1.1, 7.3]). The median OS in HPV-negative/EphrinB2-positive patients was 10.9 months (95% CI [2.0, 13.7]). The most common toxicities were hypertension, transaminitis, and fatigue.

The study concluded that the combination of sEphB4-HSA and pembro has a favorable toxicity profile and demonstrates significant activity, particularly among HPV-negative EphrinB2-positive patients with HNSCC.

This work was supported by a research grant from Merck and by the National Cancer Institute’s USC Cancer Center Support Grant (P30 CA014089).


Jackovich A, Gitlitz BJ, Tiu-Lim JWW, et al. (2024). “Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.” Oncotarget. 2024;15:444-458. Published 2024 Jul 10. doi:10.18632/oncotarget.28605

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