MSD, Moderna skin cancer vaccine scores historic phase 3 win

MSD (known as Merck in the United States and Canada) and Moderna have announced positive phase 3 results for intismeran autogene, an mRNA-based individualised neoantigen therapy (INT) for melanoma, in combination with Keytruda (pembrolizumab).

In addition to advancing an important asset for Moderna, the readout also represents the first positive phase 3 data for an INT or for an mRNA-based cancer vaccine. The trial met its primary endpoints in of recurrence-free survival (RFS) and a key secondary endpoint of distant metastasis-free survival (DMFS).

"Despite advances in the adjuvant treatment of melanoma, many patients remain at risk of recurrence and disease progression following surgery. That’s why we’re excited about the results from the Phase 3 INTerpath-001 trial, demonstrating that intismeran in combination with KEYTRUDA has the potential to further reduce the risk of recurrence or death for these patients compared to KEYTRUDA alone, standard-of-care immunotherapy," Dr Shweta Jain, VP of oncology clinical research, said in an emailed statement. "Individualised neoantigen therapies (INTS) are designed around the unique biology of each patient's tumour, with the goal of helping the immune system recognise and respond to cancer more effectively.”

More details about the results will be presented at an upcoming medical meeting. This data will also allow MSD and Moderna to begin to engage with FDA and other regulators about bringing this combination to the clinic. It adds to a growing body of evidence including a phase 2b trial, KEYNOTE-942, which showed a 49% reduction in the risk of disease progression or death.

Intismeran autogene is a personalised vaccine, derived from sampling a patient's tumour to determine its unique mutational signature. This is then used to code up to 34 cancer neoantigens that then prime the immune system to attack the tumour cells.

The news led to a huge jump in Moderna's share price, with the stock nearly doubling. Analysts have suggested that, if approved, the mRNA-4157 vaccine could generate billions of dollars in sales in its own right, but would also pave the way for Moderna's broader mRNA-based neoantigen vaccine pipeline, which also has trials running in lung, kidney, and bladder cancer.

"'This feels like a true watershed moment for cancer immunotherapy," said Trevor Polischuk lead portfolio manager at healthcare investor the Worldwide Healthcare Trust. "The significance goes well beyond melanoma: for the first time, a randomised Phase 3 trial has validated the idea that we can sequence an individual patient’s tumour, build a personalised mRNA therapy against its unique mutations, and meaningfully improve outcomes on top of an established standard of care. If the magnitude and durability of benefit hold up in the full dataset, today’s result could mark the transition of personalised cancer vaccines from a compelling scientific concept into a major new therapeutic platform."

It's welcome news for a company whose public struggles with the US government over its flu and COVID-vaccines may have spooked investors this year. The company has already begun building up it's commercial machinery in preparation for this and other launches.

“These Phase 3 findings represent a pivotal moment for the field of cancer research," said Stéphane Bancel, CEO of Moderna. "For many years, the idea of creating an mRNA treatment designed specifically for an individual patient's cancer was aspirational. We are now helping turn that vision into a reality. Together with Merck, we have started to demonstrate the transformative potential of this technology to address critical unmet needs in the adjuvant melanoma setting. We are deeply grateful to the patients, investigators, and study teams whose contributions make this progress possible.”