Melanoma vaccine in clinical trials at University of Iowa
University of Iowa Health Care is one of the first sites in the U.S. to participate in a phase 3 clinical trial to test a new, personalized vaccine for patients with high-risk melanoma.
The study will combine individualized mRNA vaccines with the immunotherapy pembrolizumab (brand name Keytruda) to determine if the combination is safe and does a better job than pembrolizumab alone at preventing melanoma from returning in people with high-risk disease.
The new vaccines were developed by Moderna and Merck and are tailored to target each patient’s unique tumor. To create the vaccine, the tumor is removed and sequenced and the genetic data is used to develop a personalized vaccine that can target several patient- and tumor-specific proteins. The vaccine will tell the patient’s immune system to target tumor cells wherever they are. Researchers hope combining the personalized vaccine with pembrolizumab, which boosts the patient’s immune response, will keep melanoma from returning.
The trial’s goal is to enroll 1089 patients with stage IIB to IV melanoma who will have their tumors surgically removed. The vaccine has minimal side effects, including mild aches, chills, and mild fever.
Yousef Zakharia, medical oncologist at the University of Iowa, Associate Professor of Medicine and Phase One Director at the Holden Comprehensive Cancer Center is enthusiastic about the trials.
“This is an exciting mRNA- based vaccine that is personalized towards the patient’s tumor itself,” said Zakharia. “As the cancer cells grow and multiply, they tend to have a lot of genetic mutation and this results in what we call new antigen. The body and the immune system look at it as a foreign body and start attacking it. Based on this mechanism, multiple vaccines are being developed, or multiple treatment options are being developed and one of them is this mRNA-based vaccine that encodes up to 34 new antigens, personalized to the patient. We take the patient’s tissue and send it out to the sponsor of this clinical trial. They do the genetic analysis of what we call next gene sequencing and they manufacture a vaccine based on that sequencing and send it back to offer it to the patient as intramuscular injections.”
The trial has recently begun phase three in the research. “Patients will be treated either with single agent immunotherapy called pembrolizumab, which is FDA approved in this setting of stage 2B and above melanoma after surgical resection. Either they will get pembrolizumab versus single agent or the combination of this pembrolizumab plus this vaccine. The idea is to see if that combination with the vaccine improves recurrence free survival, meaning delaying the recurrence or decrease the chances of recurrence of melanoma.”
The first time many people may have heard of mRNA vaccines was during the COVID outbreak. “Certainly COVID is the most common mRNA vaccine or known vaccine,” said Zakharia. “This has similar mechanisms-based mRNA vaccine where (we) utilize the tumor antigens and try to stimulate the antibody immune response towards those specific antigens. By stimulating those personalized reactions to this vaccine antigens, the immune system starts recognizing the tumor itself and starts attacking it.”
Creating the personalized vaccine doesn’t mean following a recipe like in a cookbook, says Zakharia. “Once we send the tissue out to the sponsor of this clinical trial, once they studied the genetic (makeup) of the tumor by doing next gene sequencing, they will be able to manufacture a vaccine based on that specific genetic sequence that was taken from the patient. They manufacture that vaccine and send it back to the treating center. Patients get started on this clinical trial treatment (of) up to nine doses of intramuscular muscle injection in combination with pembrolizumab immunotherapy, which is already FDA approved for this indication.”
While the trial is currently centered on melanoma, there are plans to expand trials to other forms of cancer. “One of the very early indications for pembrolizumab is metastatic melanoma,” said Zakharia. “This immunotherapy targeting what we call PT1 or PD1 inhibitors made a revolution in the cancer world in general. All these studies have started in melanoma before making themselves into other types of cancers.” Research is starting soon on using the vaccine to treat another form of cancer. “There are ongoing clinical trials with this vaccine and we are opening one study here in bladder cancer in the same setting after surgeries. It is being studied in other types of cancers too after surgery.
It will still be a few years before the immunization is available for wider use. “It will take a long time at least my anticipation at least maybe three, four, five years before we learn about the results. If the results are encouraging enough, then they become FDA approved and patients can be potentially eligible for it. This is a lengthy procedure that takes years and years in all before it becomes FDA approved.
Even though it won’t be available for a few years, Zakharia believes patients should talk with their doctors about the option. “I think this is very exciting trial, very innovative mechanism of action. I would encourage all our patients in the state of Iowa and surrounding states to seek out these types of innovative treatment options. That’s how we advance science and that’s how we increase our patients’ therapeutic options.”
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