Improved efficacy of pembrolizumab when combined with sEphB4-HSA in HPV-negative EphrinB2-positive HNSCC

“Future development for sEphB4-HSA in HNSCC is likely to focus on patients with HPV-negative disease where there is greatest need to improve on the outcomes with pembrolizumab monotherapy.”

BUFFALO, NY- July 22, 2024 – A new research paper was published in Oncotarget's Volume 15 on July 10, 2024, entitled, “Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma.”

Patients with relapsed or metastatic head and neck squamous cell carcinoma (HNSCC) after primary local therapy have low response rates with cetuximab, systemic chemotherapy or check point inhibitor therapy. Novel combination therapies with the potential to improve outcomes for patients with HNSCC is an area of high unmet need.

In this new study, researchers Alexandra Jackovich, Barbara J. Gitlitz, Justin Wayne Wong Tiu-lim, Vinay Duddalwar, Kevin George King, Anthony B. El-Khoueiry, Jacob Stephen Thomas, Denice Tsao-Wei, David I. Quinn, Parkash S. Gill, and Jorge J. Nieva from Rutgers New Jersey Medical School and the University of Southern California conducted a phase II single-arm clinical trial of locally advanced or metastatic HNSCC patients treated with a combination of soluble EphB4-human serum albumin (sEphB4-HSA) fusion protein and pembrolizumab after platinum-based chemotherapy with up to 2 prior lines of treatment. 

“sEphB4-HSA in combination with pembrolizumab has a safety profile similar to what has been observed previously with no overlapping toxicity.”

The primary endpoints were safety and tolerability and the primary efficacy endpoint was overall response rate (ORR). Secondary endpoints included progression free survival (PFS) and overall survival (OS). HPV status and EphrinB2 expression were evaluated for outcome.

Twenty-five patients were enrolled. Median follow up was 40.4 months (range 9.8 – 40.4). There were 6 responders (ORR 24%). There were 5 responders in the 11 HPV-negative and EphrinB2 positive patients, (ORR 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). Median OS in HPV-negative/EphrinB2 positive patients was 10.9 months (95% CI 2.0, 13.7). Hypertension, transaminitis and fatigue were the most common toxicities.

“The combination of sEphB4-HSA and pembrolizumab has a favorable toxicity profile and favorable activity particularly among HPV-negative EphrinB2 positive patients with HNSCC.”

Continue reading: DOI: https://doi.org/10.18632/oncotarget.28605 

Correspondence to: Alexandra Jackovich, Jorge J. Nieva

Emails: atj41@njms.rutgers.edu, jorge.nieva@med.usc.edu 

Keywords: EphrinB2, EphB4, HNSCC, pembrolizumab, HPV-negative

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