Commentary

Video

Dr Leidner on the DPV-001 Vaccine Plus PD-1 Inhibition in Metastatic HNSCC

Rom S. Leidner, MD, discusses the rationale for studying DPV-001 plus PD-1 inhibition in advanced or metastatic head and neck squamous cell carcinoma.

Rom S. Leidner, MD, medical oncologist, Providence Cancer Institute Franz Clinic, member, Earle A. Chiles Research Institute, Providence Health, discusses the background for investigating the multivalent vaccine DPV-001 in combination with PD-1 inhibition with or without a GITR agonist in patients with advanced or metastatic head and neck squamous cell carcinoma (HNSCC).

Notably, this combination was evaluated in the phase 1 GITRVax trial (NCT04470024), findings from which were presented at the 2024 AACR Annual Meeting. Leidner begins by stating that he and other co-investigators developed the multivalent autophagosomal vaccine in-house. This vaccine is groundbreaking because it challenges a longstanding paradigm in tumor immunology that has persisted for over 50 years, leading to new insights into cancer’s “dark matter,” he explains.

One of the first findings that stood out in the GITRVax trial was the vaccine’s bioactivity, he continues. In both arms of the study, investigators observed early signals of immune bioactivity, coupled with a greater breadth and frequency of immune-related adverseeffects than typically seen with PD-1 blockade alone in patients with HNSCC, according to Leidner. These immune responses were soon followed by corroborative clinical outcomes, underscoring the critical importance of linking bioactivity with clinical efficacy, Leidner reports.

This connection between bioactivity and clinical response is essential, as most researchers now believe that successful combinatorial strategies with immunotherapy will likely involve some level of toxicity, which, although manageable, serves as a necessary indicator of treatment effectiveness, he says. Without such bioactive readouts, there is growing skepticism about the potential success of these therapies, Leidner says. The observed immune bioactivity in trials with DPV-001 validates the vaccine’s therapeutic potential and highlights the importance of these signals in advancing immunotherapy strategies, he notes. This work opens new avenues for understanding and exploiting the complex mechanisms underlying tumor immunity, offering hope for more effective cancer treatments in the future, Leidner concludes.

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