Celeritas Insights

Therapeutic cancer vaccines have been in development for decades, mostly with disappointing results, but are seeing renewed interest for development over the past few years. So far, the only product that has made it to market is the dendritic cell vaccine, Dendreon Pharmaceuticals’ Provenge (sipuleucel-T), which received FDA approval in 2010 for the treatment of patients with metastatic castration-resistant prostate cancer. Despite the approval, Provenge has not done well commercially and it has received the negative opinion of many physicians revolving around complicated administration, high price tag, and meager overall survival (OS) benefit.

Cancer vaccines can be classified in many different ways, but some overarching themes are peptide-based vaccines, nucleic-acid-based vaccines, and cell-based vaccines. Furthermore, these categories can be separated in off-the-shelf, or personalized. Currently, the most advanced pipeline candidate is Moderna’s personalized mRNA vaccine mRNA-4157 which is in Phase III trial for the adjuvant treatment of melanoma.

In 2024’s AACR conference, more encouraging signals for cancer vaccines were presented. Diakonos Oncology’s personalized dendritic vaccine DOC1021 demonstrated an 88% OS for patients with unmethylated glioblastoma in a Phase I study of 16 patients, which compelled the company to plan a Phase II study. Also, BioNTech/Genentech’s personalized mRNA vaccine autogene cevumeran showed delayed tumor recurrence in patients with resected pancreatic cancer, which prompted the initiation of a Phase II study.

The main advantage of therapeutic cancer vaccines is their mostly excellent tolerability, which makes them ideal combination partners. Given their mostly low efficacy, we believe current vaccine approaches are better suited to the early-stage setting to prevent disease recurrence. However, companies such as Geneos Therapeutics and PDC*line Pharma are taking the riskier approach of treating advanced-stage disease. Geneos’ personalized DNA vaccine GNOS-PV02 is attempting to improve Keytruda’s efficacy in second-line hepatocellular cancer with the Phase I/II study. PDC*line Pharma’s cell-based off-the-shelf vaccine PDC*lung01 is attempting to improve anti-PD-1 efficacy in patients with metastatic non-small cell lung cancer patients with a PD-L1 score of over 50% in the Phase I/II PDC-LUNG-101 study.

The above represents plenty of positive news for therapeutic cancer vaccines which will undoubtedly result in increased clinical development in the near future.

By Sakis Paliouras, PhD

References:

[1] Nature article on therapeutic cancer vaccines

[2] Moderna and Merck announcement on mRNA-4157 vaccine

[3] Diakonos Oncology's Phase I study on personalized dendritic vaccine

[4] BioNTech/Genentech's Phase II study on personalized mRNA vaccine

[5] Geneos Therapeutics' Phase I/II study on personalized DNA vaccine

[6] PDC*line Pharma's Phase I/II study on cell-based off-the-shelf vaccine