London | An international clinical trial testing a novel cancer immunotherapy, which may prevent skin cancer from recurring, has recruited its first patient in Britain this week.
The mRNA-based technology, the vaccine tech used for some COVID vaccinations, is aimed at people who have already had high-risk melanomas – the most serious form of cancer – removed.
For the trial, University College London Hospitals (UCLH) doctors are giving it alongside another drug, pembrolizumab or Keytruda, that also helps the immune system kill cancer cells.
One of the first patients to sign up for the trial is British musician Steve Young, 52, from Hertfordshire, east England, who was diagnosed with stage II melanoma, which was removed.
“I feel lucky to be part of this clinical trial. Of course, I did not feel so lucky when I was diagnosed with skin cancer, in fact, it came as quite a shock, but now that I’ve had treatment, I’m keen to ensure it does not recur. This is my best chance at stopping the cancer in its tracks,” Young said.
The personalised treatment works by instructing the body to make up to 34 proteins, each targeting “neoantigens” identified by gene sequencing and thought to be driving the cancer in that particular patient. The neoantigens are proteins found only on the cancer cells, and the individualised neoantigen therapy is designed to prime the immune system to attack the tumour cells in each patient, while Keytruda blocks an immunological “brake” that protects the cancer.
“The idea behind this immunotherapy is that, by prompting the body to make these proteins, it can prepare the immune system to quickly identify and attack any cancer cells bearing them, with the aim of preventing recurrence of melanoma,” said University College London medical oncologist Heather Shaw, the national coordinating investigator of the new trial.
The new Phase 3 clinical trial, being led by UCLH, is evaluating the combination of mRNA-4157 (V940) and Keytruda (pembrolizumab) versus a current standard of care (pembrolizumab) as a risk-reducing treatment option for patients with resected high-risk, stage IIB to IV melanoma.
It follows a successful Phase 2 study, which found that in patients with stage IIIB to IV resected melanoma, this treatment option almost halved the risk of cancer recurrence or death after three years compared with treatment with Keytruda alone among patients with advanced melanomas following surgical removal of cancer.
Melanoma is characterised by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with nearly 3,25,000 new cases diagnosed worldwide in 2020. In the UK, melanoma is the fifth most common type of cancer, accounting for about 8,400 new cases every year.
The mRNA technology was developed by Moderna in conjunction with Merck Sharp and Dohme (MSD), which used the learning from COVID research development and is expected to contribute to new treatments for cancer patients.
Researchers are now hoping that the Phase 3 study, which is running in several sites across the UK, will confirm the findings of the earlier trial. The Phase 3 trial, named INTerpath-001, will enrol around 1,089 patients across the world. The primary outcome measure is recurrence-free survival, with overall survival and metastasis-free survival as secondary outcomes.
V940-001 is a Phase 3 global, randomised, double-blind, placebo- and active-comparator-controlled study. This means Steve Young knows he is receiving Keytruda, but will not find out if he is getting the personalised cancer treatment or a placebo.
