Merck (known as MSD outside the United States and Canada) and Moderna have announced positive topline results from the phase 3 INTerpath-001 trial evaluating intismeran autogene, in combination with Keytruda (pembrolizumab), to treat patients with completely resected stage IIB-IV melanoma.
Intismeran autogene is an mRNA-based individualised neoantigen therapy (INT) designed specifically for each patient based on the unique set of mutations within their tumour to train and activate the immune system to recognise and fight cancer.
This is the first and only combination regimen to demonstrate statistically significant and clinically meaningful improvements in recurrence-free survival (RFS) and distant metastasis-free survival (DMFS) compared to Keytruda alone for patients with resected melanoma.
Melanoma, one of the deadliest forms of skin cancer, is characterised by the uncontrolled growth of pigment-producing cells. The rates of melanoma have been rising over the past few decades, with more than 330,000 new cases diagnosed worldwide in 2022.
In the US, skin cancer is one of the most common types of cancer diagnosed and melanoma accounts for a large majority of skin cancer deaths. It is estimated there will be about 112,000 new cases of melanoma diagnosed and over 8,500 deaths resulting from the disease in the US in 2026 alone.
Despite advances in treatment, patients with resected melanoma remain at risk of disease recurrence, which most often occurs within the first two years. The majority of recurrences are metastatic rather than localised, highlighting the ongoing need for treatment approaches that may help reduce the risk of recurrence and improve long-term outcomes.
“These results represent a landmark moment for adjuvant melanoma treatment. This is the first phase 3 study to show that intismeran, a treatment designed based on the unique mutational ‘fingerprint’ of a patient’s own tumour, given in combination with pembrolizumab, can reduce the risk of recurrence or death in patients with completely resected stage IIB-IV melanoma compared to Keytruda alone,” said Professor Georgina Long, the study’s principal investigator and medical director of Melanoma Institute Australia, Chair of Melanoma Medical Oncology and Translational Research at the University of Sydney.
“By intervening earlier in the course of disease, when many cancers are considered most treatable, the goal of adjuvant therapy given after surgery is to increase the possibility of cure for more patients,” said Dr Dean Y. Li, president, Merck Research Laboratories. “These first phase 3 findings for intismeran in combination with Keytruda as adjuvant therapy reinforce the promise of a more personalized approach to cancer treatment. We believe individualized neoantigen therapies have the potential to redefine how patients with completely resected stage IIB-IV melanoma are treated.”
“These phase 3 findings represent a pivotal moment for the field of cancer research. 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,” said Stéphane Bancel, CEO of Moderna. “Together with Merck, we have started to demonstrate the transformative potential of this technology to address critical unmet needs in the adjuvant melanoma setting.”