Pharmaceutical companies MSD and Moderna have announced a positive outcome for their phase 3 trial comparing an investigational and individualised mRNA vaccine with anti-PD-1 therapy in melanoma patients.
The combination of intismeran autogene and pembrolizumab (Keytruda) was found to result in “statistically significant and clinically meaningful improvements” in recurrence-free survival and distant metastasis-free survival compared to pembrolizumab alone – although no actual data were presented.
“This represents the first positive phase 3 readout for an individualized neoantigen therapy and for an mRNA-based cancer therapy, as well as the first phase 3 study to demonstrate a clinically meaningful improvement over Keytruda alone, a standard-of-care immunotherapy, in the adjuvant setting for patients with resected melanoma,” said MSD and Moderna in a joint statement.
Australian melanoma expert Professor Georgia Long, who served as the principal investigator on the trial, said the findings represented 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 the medical director of Melanoma Institute Australia and Chair of Melanoma Medical Oncology and Translational Research at the University of Sydney.
“Intismeran in combination with pembrolizumab has the potential to establish a new treatment paradigm in the adjuvant melanoma setting, helping patients remain cancer-free for longer.”
Intismeran autogene is a first-of-its-kind investigational mRNA-based individualised neoantigen therapy (INT) developed by MSD and Moderna. It is designed and produced from a sample of each individual patient’s tumour to uncover the unique mutational “fingerprint” of the cancer and generate an anti-tumour immune response.
“Each therapy consists of a synthetic mRNA coding for up to 34 neoantigens and is tailored to the unique biology of an individual patient’s tumour,” MSD and Moderna said in a statement. “Upon administration, the RNA-encoded neoantigen sequences are translated in the body and presented to the immune system, a key step in generating specific T-cell responses against cancer cells.”
INTerpath-001 was a randomised, double-blind international phase 3 trial that sought to evaluate the safety and efficacy of the combination of intismeran and pembrolizumab compared to pembrolizumab alone in patients with high-risk (stage IIB-IV) cutaneous melanoma.
There were 1137 patients recruited as part of the trial. After undergoing complete surgical resection of their melanoma, patients were randomised in a 2:1 fashion to receive either intismeran (1mg every three weeks for up to nine doses) and pembrolizumab (400mg every six weeks for up to nine cycles) or pembrolizumab alone. Patients were treated until disease recurrence, they experienced an unacceptable level of toxicity, or for approximately 56 weeks, whichever came first.
The primary endpoint of the INTerpath-001 trial was recurrence-free survival – defined as the time from randomisation to any disease recurrence (local, locoregional, or distant) – or death due to any cause. Select secondary endpoints include overall survival, distant metastasis-free survival, safety, tolerability, and quality of life.
Related
The phase 3 results add to the five-year follow-up data from the phase 2b KEYNOTE-942/mRNA-4157-P201 trial presented at the ASCO Annual Meeting earlier this year, which saw the combination therapy reduce the likelihood of recurrence or death by 49% and reduce the likelihood of distant metastasis or death by 59% compared to pembrolizumab alone in patients with high-risk, resected melanoma.
Dr Dean Y. Li, president of MSD Research Laboratories, said individualised therapies such as intismeran could change the way patients with resected melanoma were treated.
“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,” he said.
Moderna CEO Stéphane Bancel was similarly positive, describing the new findings as “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,” they told media.
“Together with [MSD], 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.”
Associate Professor Seth Cheetham, head of the Australian mRNA Cancer Vaccine Centre and director of the National Biologics Facility at the University of Queensland, said that being able to deliver this kind of therapy at a large enough scale to ensure patients throughout the community could access it would be a challenge for the near future.
“While previous personalised medicines match patients to the right drug, this is the first to create an entirely new drug for each patient,” Professor Cheetham said.
“The trial represents a landmark in personalised cancer medicine and is the start of a wave of new studies to bring this technology to patients with other diverse types of cancer.”
The complete results of the INTerpath-001 trial will be presented at upcoming international conferences and form the basis of MSD and Moderna’s submissions to regulatory bodies such as the US Food and Drug Administration and Australia’s Therapeutic Goods Association.
The two companies will also continue to advance their INTerpath clinical development program, where they are collecting further data on the safety and efficacy of the intismeran in combination with pembrolizumab and other anti-cancer therapies – and as a monotherapy – across other research studies.
“The INTerpath program currently consists of nine total phase 2 and phase 3 clinical trials across multiple tumour types and stages of disease, including melanoma, non-small cell lung cancer (NSCLC), bladder cancer, and renal cell carcinoma,” the two companies said in their joint statement.
“Additional clinical studies include the phase 2b KEYNOTE-942/mRNA-4157-P201 trial in adjuvant melanoma and a phase 1 study exploring adjuvant pancreatic ductal adenocarcinoma, perioperative gastric carcinoma, and perioperative NSCLC.”
The post ‘Landmark moment for adjuvant melanoma treatment’: Long appeared first on Medical Republic.
Add Comment