Is Moderna and MSD’s melanoma combo a true ‘penicillin moment’ in cancer treatment?

Pharma News: Moderna and MSD unveiled findings of a new mRNA-based vaccine for melanoma, labelled in the media as ‘the penicillin moment’ for cancer treatment.

Initial results from the Phase 2 KEYNOTE-942 clinical trial* showed that the vaccine developed by Moderna in combination with MSD’s anti-PD-1, Keytruda, significantly reduced the risk of cancer recurrence or death for melanoma patients.

“Melanoma vaccines have been worked on for decades, albeit with little efficacy. However, this is one of the first that has shown promising enough results to proceed to a larger definitive study,” said Professor Anthony Joshua, who is a medical oncologist and Head of Clinical Science at the Garvan Institute of Medical Research, as well as a Conjoint Professor at UNSW Medicine & Health.

It all sounds exciting but don’t be lining up for your jab, experts warn. This vaccine is designed for patients with existing melanoma, to prevent tumour recurrence after it has been surgically removed.  

“The Moderna vaccine targets a number of tumour mutations which are highly specific to the individual being treated. These mutations are BH1 analysed and chosen to give the greatest immune response and developed into a vaccine which is personalised for the patient,” said Dr John Frew, who is a dermatologist at Liverpool Hospital and Conjoint Senior Lecturer at UNSW Medicine & Health.

Unfortunately, a common melanoma vaccine is unlikely to be effective due to individual differences between patients.

“Each melanoma has a large number of genetic mutations that are distinct from normal skin tissue. As a result, melanomas from two people are likely to be genetically quite divergent,” said Dr Sarah Sasson, Clinical Immunologist/Immunopathologist and Scientia Senior Lecturer at the Kirby Institute, UNSW.

“This means making a ‘one size fits all’ melanoma vaccine might have a low overall efficacy in a large number of patients living with melanoma.”

The Phase 2 clinical trial involved 157 patients with advanced melanoma which had been surgically removed. One group of patients received the melanoma vaccine in combination with MSD’s immunotherapy drug Keytruda, and the other group received only Keytruda. According to the data, treatment with the vaccine reduced the risk of cancer recurrence or death by 44%.

“It’s certainly exciting… But these are early results and the trial is quite small, and this concept needs to be tested further. It will also be important to see how and if the vaccine did indeed generate an immune response against the tumour and how long it lasts,” Prof. Joshua said.

This year Moderna and MSD plan to initiate a Phase 3 clinical trial which may bring this much-needed treatment closer for melanoma patients.

“It is an excellent step in the right direction using new personalised medicine technology, which has come to us as a silver lining out of the COVID-19 pandemic and experience with mRNA vaccines,” Dr Frew added.

“It certainly opens up new doors to novel therapeutics and novel adjuvant therapies – but it is as yet unclear whether this is a true ‘penicillin moment’.”

*Phase 2b KEYNOTE-942/mRNA-4157-P201 trial of mRNA-4157/V940, an investigational personalized mRNA cancer vaccine, in combination with KEYTRUDA, MSD’s anti-PD-1 therapy, demonstrated a statistically significant and clinically meaningful improvement in the primary endpoint of recurrence-free survival (RFS) versus KEYTRUDA alone for the adjuvant treatment of patients with stage III/IV melanoma following complete resection. Adjuvant treatment with mRNA-4157/V940 in combination with KEYTRUDA reduced the risk of recurrence or death by 44% (HR=0.56 [95% CI, 0.31-1.08]; one-sided p-value=0.0266) compared with KEYTRUDA alone.