Oncotarget

Research Papers:

Improved efficacy of pembrolizumab combined with soluble EphB4-albumin in HPV-negative EphrinB2 positive head neck squamous cell carcinoma

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 _

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Oncotarget. 2024; 15:444-458. https://doi.org/10.18632/oncotarget.28605

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Abstract

Alexandra Jackovich1,2, Barbara J. Gitlitz1,2, Justin Wayne Wong Tiu-lim1,2, Vinay Duddalwar1,2, Kevin George King1,2, Anthony B. El-Khoueiry1,2, Jacob Stephen Thomas1,2, Denice Tsao-Wei1,2, David I. Quinn1,2, Parkash S. Gill1 and Jorge J. Nieva1,2

1 Rutgers New Jersey Medical School, Newark, NJ 07103, USA

2 Division of Medical Oncology, University of Southern California, Los Angeles, CA 90007, USA

Correspondence to:

Alexandra Jackovich, email: [email protected]
Jorge J. Nieva, email: [email protected]

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

Received: June 06, 2024     Accepted: June 27, 2024     Published: July 10, 2024

Copyright: © 2024 Jackovich et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

ABSTRACT

Objective: 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.

Methods: This is 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. 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.

Results: 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.

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


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