MUHC patients among the first in the world to enroll in mRNA individualized treatment trials for lung cancer

The Research Institute of the McGill University Health Centre is at the forefront of clinical trials in precision cancer medicine, testing a novel technology similar to that used in mRNA COVID-19 vaccines.

The COVID-19 pandemic led to massive investment in research, enabling the rapid development of the first messenger RNA (mRNA) vaccines. This revolutionary technology, which teaches cells how to make a protein that triggers the targeted immune response, is now being tested to combat lung cancer—the leading cause of cancer death worldwide—in two global Phase 3 clinical trials.

Thanks to the swift and effective mobilization of teams at the Centre for Innovative Medicine of the Research Institute of the McGill University Health Centre (The Institute), the leadership of Dr. Jonathan Spicer and the collaboration of several clinical teams, MUHC patients are the first in Canada, and among the first in the world, to participate in these randomized clinical trials evaluating V940 (mRNA-4157), an individualized neoantigen therapy based on mRNA technology and developed through a partnership between Merck, known as MSD outside the United States and Canada, and Moderna. This new investigational therapy is tested in combination with immunotherapy in patients with stage II or III non-small cell lung cancer (NSCLC)—the most common form of lung cancer—who have undergone surgery.

“Over the past few weeks, we have been the first site in Canada to treat a patient enrolled in INTerpath-002 and we have recruited the first patient worldwide to start INTerpath-009—two Phase 3 placebo-controlled trials testing V940 individualized neoantigen therapy in combination with pembrolizumab, an immunotherapy agent that strengthens the ability of the body’s immune system to detect and fight tumour cells,” says Dr. Spicer, thoracic surgeon at the Montreal General Hospital of the MUHC, Scientist in the Cancer Research Program at The Institute and Medical Director of the McGill Thoracic Oncology Network. “I am optimistic that this effort could be transformative for patients with resectable NSCLC, given its individualized sequencing approach and the clear data supporting its conceptual impact.” 

The power of RNA messenger technology

Previously, mRNA medicines, such as vaccines developed for COVID-19, were made to provide the body with the necessary instructions to produce a protein specific to the targeted virus so that the organism can develop antibodies to attack the virus if it becomes infected.

In the case of V940, the technology is being tested for therapeutic rather than preventive purposes. After removal, the tumour is analyzed in the laboratory by molecular sequencing. The aim is to identify the genetic mutations present only on a unique patient’s tumour (and not in his or her germline or personal DNA), as well as the proteins derived from it, that are known as neoantigens. This step enables the development of a mRNA with sequences specific to these neoantigens. The resulting V940 is then given to the patient with an injection, in order to enable the patient’s immune system to seek out and attack any cancer cells that may still be lurking in different parts of the body. 

“We know that patients who have residual disease in their tumours specimen are at higher risk of recurrence. We have a true hope that this therapy, designed to train and activate an antitumour immune response based on the unique mutational signature of the patient’s tumour, will improve their outcomes,” adds Dr. Spicer.

“Our genes are made of DNA. When cancer evolves, it’s usually due to some mutation that occurs in the DNA of the tumour cells, which get transcribed and translated into abnormal proteins (neoantigens),” he explains. “Immunotherapy helps awaken the immune system’s ability to find those cells, but in an imperfect way. Our hope is that this new individualized neoantigen therapy will prime the immune system to find and kill cells that our scanners can’t detect and that carry these neoantigens, wherever they are in the body.”

Different studies, one novel therapy

In the INTerpath-002 trial, patients first get surgery, followed by chemotherapy. After having received at least one cycle of chemotherapy, they are randomly assigned to the trial treatment group (pembrolizumab [KEYTRUDA®] with the V940 individualized neoantigen therapy) or to the control group (receiving pembrolizumab with a placebo). 

Those enrolled in INTerpath-009, which has recently opened, will follow a slightly different protocol. They will first receive pre-operative chemotherapy and pembrolizumab, before undergoing surgery. If cancerous cells are found in their tumour, after its removal, they will be randomly assigned to either the treatment or control group. 

The INTerpath-002 and INTerpath-009 trials follow the Phase 2b KEYNOTE-942/mRNA-4157-P201 trial, which tested the combination of pembrolizumab and V940 in melanoma patients, with positive results. 

Building on a vision, teamwork and leadership

“The fact that we have been able to open these two trials is a testament to the dedication and competitiveness of our teams at the Centre for Innovative Medicine, but also to the hard work of the thoracic team who has actively contributed to the development of perioperative immunotherapy. Let’s not forget the excellent collaboration of the dedicated research team of nurses, coordinators and administrators and all the different people involved in patient care at the MUHC, including pharmacists, oncologists and radiation oncologists, surgeons, pathologists, pulmonologists and nurses,” says Penny Chipman, Manager of Oncology Research at The Institute’s Centre for Innovative Medicine.

This effort builds on previous immunotherapy trials in which Dr. Spicer played a pivotal role, most notably the KEYNOTE-671 trial which showed, in its most recent interim analysis, that pembrolizumab, used in combination with chemotherapy before and after surgery in people with operable, early stage NSCLC, extended patients’ lives without compromising their quality of life (as published in The Lancet).

“We pride ourselves on providing access to some of the most advanced experimental treatments before anyone else in the world. The faster we can offer clinical trials to our patients, the faster science advances and new therapies are approved by government agencies and made available to those who need them,” says Dr. Louise Pilote, Director (interim) of the Centre for Innovative Medicine, Co-Chair of Accelerating Clinical Trials—Clinical Trial Unit and Deputy Director of The Institute.


Media contact
Fabienne Landry
Communications coordinator, Research, MUHC
[email protected]