Skin cancer | World’s first mRNA vaccine for melanoma being tested in patients

In previous editions of SCORacle, we have covered a number of new developments in healthcare, particularly with regard to vaccines and cancer treatments. It seems there are regular breakthroughs being reported in the treatment of the conditions we see frequently at both underwriting and claims stage. 

Technology such as mRNA vaccines, the use of artificial intelligence and the ongoing breakthroughs in treatments such as immunotherapy and personalised medicine mean the frequency of these developments is increasing. 

As insurers and reinsurers that develop products such as critical illness, terminal illness and income protection, we have a responsibility to stay informed on such developments and to understand how they may affect how we do things, from underwriting and claims to policy definitions and product design, not to mention understanding long-term trends so that we can keep our policies competitively priced.

This article highlights a further development in the use of vaccines being used to treat patients with melanoma. In a remarkable breakthrough, British patients are participating in trials for the world’s first personalised mRNA cancer vaccine designed specifically for melanoma. 

Melanoma is the fifth most common cancer in the UK, with approximately 16,000 cases diagnosed each year, accounting for around 4% of all new cancer cases. Approximately 1,000 new cases of malignant melanoma are diagnosed each year in the Republic of Ireland alone. In addition, cases of melanoma are on the rise, particularly affecting men. 

How does it work?

Rather than having an “off-the-shelf” treatment used for many patients, this innovative vaccine is custom-built for each patient. It harnesses the power of mRNA technology to instruct the body’s immune system to identify and combat cancer cells. Although trials are currently focused on melanoma, it has the potential to extend beyond melanoma, with implications for bladder, lung, and kidney cancers.

Once biopsied, a tumour sample is sequenced, and artificial intelligence assists in creating an individualised neoantigen therapy (INT). Unlike a generic vaccine, this therapy is precisely tailored to the patient’s unique cancer type. mRNA vaccines for cancer typically use an individual’s own cancer cells to produce the mRNA, which is then injected back into the patient to stimulate an immune response against the cancer. This approach is known as “personalised cancer immunotherapy”, and it has the potential to be highly effective because the vaccine is specifically tailored to a person’s own unique cancer cells. Our SCORacle article in April 2023, ‘mRNA vaccines – focus back to cancer after COVID-19’ explains this in detail.

Neoantigens are unique proteins or peptides found on the surface of cancer cells. Unlike normal cells, cancer cells often produce abnormal proteins due to mutations in their DNA. These neoantigens serve as “flags” that the immune system can recognise as foreign. INT leverages the body’s immune system to target and destroy cancer cells. Researchers identify neoantigens specific to an individual patient’s tumour as they are like personalised fingerprints for the cancer.

For this particular vaccine, a sample of the patient’s tumour is sequenced to identify genetic mutations. Advanced algorithms will then predict which mutated proteins will generate neoantigens and based on these predictions, a personalised mRNA vaccine is created. Once administered, the vaccine instructs the patient’s immune cells (T-cells) to recognise and attack cancer cells bearing these neoantigens. SCOR have previously released publications discussing Immunotherapy (Immunotherapy: Winning the war against cancer | SCOR) and treatments for melanoma have already seen significant developments with improved mortality. However, there are differences between INT vaccines and treatments using checkpoint inhibitors.

Checkpoint inhibitors are drugs that block certain proteins (such as PD-1 or CTLA-4) that prevent immune responses. Checkpoint inhibitors work by blocking checkpoint proteins from binding with their partner proteins. This switches back on the body’s immuno-surveillance capabilities which are turned off when cancer develops, thus allowing the T-cells to kill cancer cells.

INT uses individually tailored vaccines, which should have a greater chance of success, as it is specifically created for the individual undergoing treatment.

What are the benefits to the patient?

INT targets only cancer-specific neoantigens, minimising damage to healthy tissues. Therefore, the side-effects are kept to a minimum. Also, as tumours evolve and mutate, the vaccine can be updated to target new neoantigens. By activating the immune system, INT aims for durable effects resulting in extended remission or preventing disease recurrence over an extended period.

Clinical Trial

The initial Phase 2 study, published in The Lancet1- Individualised neoantigen therapy mRNA-4157 (V940) plus pembrolizumab versus pembrolizumab monotherapy in resected melanoma (KEYNOTE-942): a randomised, phase 2b study - ScienceDirect demonstrated promising results. It showed people with high-risk melanomas who received the vaccine alongside immunotherapy drug Keytruda, were 49% less likely to die or have their cancer come back after three years than those who just had Keytruda.

An expanded Phase 3 trial has recently launched, and it aims to validate the efficacy and safety of INT on a larger scale. This phase of the global trial will include a wider range of patients, and researchers are hoping to recruit around 1,100 people.

At least 60 to 70 patients across eight UK centres are set to be recruited, and the twin therapy combination will also be tested in lung, bladder and kidney cancer.

The trial is being conducted at University College London Hospital (UCLH), with support from the UK Vaccine Innovation Pathway (VIP). The VIP streamlines clinical trials for personalised mRNA vaccines, demonstrating the UK’s leadership in advancing innovative cancer treatments.

Our CMO view

SCOR Oncology CMO, Professor Eric Raymond makes the following comments.

“To date, vaccinations have been used for a long time for the prevention of cancer such as HPV-induced cervical carcinoma, anal and head and neck tumours and squamous cell carcinoma. 

Currently, mRNA vaccines are entering later stages of clinical development, aimed at triggering the recognition of cancer cells by immune effector cells, and may be soon able to challenge standards of care. mRNA vaccinations represent a major innovation for patients who are not sensitive to current standards of care, and who progressed or relapsed following chemotherapy and classical immunotherapy.”

Significance

INT represents a major leap toward precision medicine, where treatments are tailored to individual patients. If successful, it could further be used to revolutionise melanoma therapy and potentially extend to other cancer types.

INT represents a powerful fusion of genomics, immunology, and personalised medicine. By harnessing the immune system’s potential, we’re inching closer to more effective and targeted cancer therapies with prolonged survival.

SCOR will continue to track the progress of this important trial and update when any new information is published.