For patients who did achieve a DCB after the vaccine, of the 20 neoantigen peptides in each vaccine, between 5 and 12 peptides were found to successfully stimulate an immune response. Cancer Therapy Advisor asked Dr Srinivasan: Is there any correlation between number of peptides that stimulate an immune response and clinical response to the vaccine?

“It [RECON] is a constantly developing platform, it is an iterative process,” explained Dr Srinivasan, who also noted that the pipeline features machine learning. “We are trying to understand more whether patients who have more immune responses will be the ones who have a better correlation to clinical outcome. It’s a very small number of patients and we do not want to make these correlations with such small numbers of patients,” said Dr Srinivasan.

Although this therapy is in the early stage of testing in human trials, results appear to indicate that the therapy was well tolerated; there were no additional toxicities observed on top of those normally seen with nivolumab treatment.

“Most patients can maintain a very active lifestyle. Patient[s] can get injection site soreness and rash and sometimes a bit of fever. Immunotherapy can have toxicities in general; nobody had any significant additional toxicity with the vaccine on this trial,” said Dr Hu-Lieskovan.

Questions also remain as to how to tease out the effect of NEO-PV-01 and that of the nivolumab treatment given throughout the trial protocol.

“All the patients received nivolumab before receiving the neoantigen-based vaccine. It is not possible to distinguish the effect of nivolumab and the effect of vaccine, particularly for melanoma, a malignant disease that is sensitive to nivolumab as a single agent,” said Dr Zheng, who observed that the clinical response could be a delayed effect of nivolumab. He also said that the vaccine could indeed be making the response to the initial nivolumab deeper—but its action could be dependent on the aforementioned pretreatment with nivolumab.

“Then, one would argue that more nivolumab treatments would also make the response deeper. Therefore, a randomized study would be warranted,” said Dr Zheng.

These early results on NEO-PV-01 can be considered promising, and the data on the patients with bladder cancer and NSCLC are expected to be presented later this year should further strengthen the evidence for the therapy. Questions remain in regard to how much of the observed therapeutic effect is due to nivolumab, what is the eventual cost of the product, and how (or if) the therapy will compete with other new treatments for advanced melanoma, such as TVEC.4

Disclosure: Lakshmi Srinivasan, PhD disclosed a financial relationship with Neon Therapeutics. For details, please see the presentation in reference 1.

Reference

  1. Hu-Lieskovan S, Ott PA, Naing A, et al. The personalized vaccine NEO-PV-01, with anti-PD-1, induces neoantigen-specific de novo immune responses in patients with advanced or metastatic melanoma: association with clinical outcomes. Presented at: American Association for Cancer Research (AACR) Annual Meeting 2019; March 29-April 3, 2019; Atlanta, GA.