The race is on to develop therapeutic cancer vaccines that could give immunotherapies an edge, and late-stage trials could soon provide more-robust data about candidates’ efficacy and safety.
Oncology remains the major focus area in R&D for large pharma companies as global spending in the area continues to grow. Immunotherapies, in particular, have quickly become some of the best-selling products on the market. Seeking ever more efficacious treatments, companies are now eyeing cancer vaccines, which experts say could be more powerful than other immunotherapies and may even provide a preventative measure against certain malignancies.
The first therapeutic cancer vaccine was approved in 2010, and Dendreon’s Provenge is still the only therapy of this type on the market. But interest in the space is growing as certain candidates enter late-stage clinical trials.
“It’s definitely a competitive area,” said Scot Ebbinghaus, vice president of clinical research at Merck, which is developing mRNA-4157/V940 in partnership with Moderna. “But competition is a good thing for patients. It makes us work harder and smarter. We look carefully at what our competitors are doing and keep this mind when we are developing our plans.”
Proving the Concept of Cancer Vaccines
Ebbinghaus explained that both cancer vaccines and immunotherapies, such as Merck’s blockbuster Keytruda (pembrolizumab), act on the T cells, which fight cancer. “The way PD-1 inhibitors work is they take the brakes off of those cells. The vaccines work by presenting tumor-specific antigens to the immune system, which activates even more anti-tumor T cells, potentially allowing pembrolizumab to have a stronger effect,” he told BioSpace.
Merck and Moderna’s vaccine is one of the most advanced candidates in development. mRNA-4157/V940 is currently being explored as a combination treatment with Keytruda, with Phase III trials underway in high-risk melanoma and non-small cell lung cancer (NSCLC). In Phase IIb trials for melanoma, the combination treatment was able to reduce the risk of recurrence or death by 49% compared to Keytruda alone.
“What we have seen so far suggests that these drugs could be really useful in patients who have had cancer surgery and preventing recurrence,” Ebbinghaus said. “This is a very large population of patients with an unmet need to reduce the risk of cancer recurrence.”
Another potential advantage of this therapeutic approach, based on the data the partners have seen so far, is that the safety profile is similar to that of standard vaccines, Ebbinghaus added. This means pain at the injection site or mild fever, which he said is preferable to the adverse events associated with chemotherapy. These milder adverse events could also allow the vaccines to be delivered in situations where a patient’s health does not allow for exposure to harsher treatments, he noted.
Some vaccine candidates in mid- to late-stage development, such as an mRNA product being pursued by BioNTech and Roche/Genentech, are being tested in combination with chemotherapy. Now in Phase II trials, the mRNA vaccine is administered along with Roche’s checkpoint inhibitor Tecentriq and chemo against pancreatic cancer.
Another company developing a portfolio of cancer vaccines is CureVac, which announced in April that it would collaborate with MD Anderson on early-stage research. A CureVac spokesperson told BioSpace over email that the company is developing two approaches: an “off-the-shelf” platform tailored to patients with specific cancer types, and a fully personalized approach that would be based on a patient’s individual tumor genomic profile.
The MD Anderson partnership is based on the first method and the tumor antigens shared across different cancer indications. The collaboration will use whole genome sequencing in combination with short- and long-read RNA sequencing to identify promising antigens, the spokesperson said, adding that the aim is to “go beyond the current state-of-the-art antigen space.”
Preventive Therapy
Along with the aforementioned therapeutic vaccines, research is also ongoing into developing preventive vaccines. The former are designed to treat an existing cancer, while the latter aim to help the immune system recognize and destroy cancer cells before they can gain a foothold in the body.
Cancer Research UK (CRUK) recently announced it would provide funding to researchers at the University of Oxford, the Francis Crick Institute and University College London to develop a preventive lung cancer vaccine. The research could lead to the first vaccine for people at high risk of developing the disease, such as current or previous smokers aged 55–74. The vaccine, known as LungVax, is based on the same technology that was employed in AstraZeneca’s COVID-19 vaccine.
Hattie Brooks, a science engagement manager at CRUK, explained how the vaccine could potentially work. “The vector has been modified to express a protein, known as a neoantigen, that appears in lung cancer cells as they first become cancerous,” Brooks told BioSpace. “LungVax will train the body that the neoantigen is a danger and that this protein is a red flag for cancer. This allows the immune system to recognize the neoantigen as a threat and destroy the cells before the cancer has had time to develop.”
Unlike some therapeutic vaccines, the preventive vaccine could be used alone in those individuals with the highest risk of developing cancer, potentially preventing the disease from occurring and negating the need for treatment. If it proves to be promising, LungVax will be moved into clinical trials. In the U.K. alone, there are 48,500 new cases of lung cancer diagnosed every year.
While preventive vaccines are still early-stage, excitement around cancer vaccines more broadly continues to grow as therapeutic vaccines move through mid- and late-stage clinical development. It will not be long before the potential of this approach is either realized or dealt a blow.
For Merck’s part, Ebbinghaus said the company has seen enough promise in the data from mRNA-4157/V940 that it is already in discussion with Moderna for further clinical programs looking ahead to 2025 and beyond.
Ben Hargreaves is a freelance science journalist based in Tosse, France. Reach him on LinkedIn.
