UI Health Care is leading a clinical trial that is demonstrating a completely new way of harnessing the immune system to fight cancer.

For decades, metastatic melanoma was one of the most challenging cancers to treat. Traditional therapies, like chemotherapy, showed limited success, especially in more advanced cases. When the immunotherapies pembrolizumab (marketed as Keytruda) and nivolumab were approved in 2014, they revolutionized cancer care, especially for melanoma, which showed high response rates. In fact, with nivolumab alone, about 40% of melanoma patients respond to the treatment. When combined with other immunotherapies, that number rises to 50%. But that still leaves half of the patients with no options. A new approach to boost the immune response is needed.

For the past six years, Mohammed Milhem, MBBS, medical oncologist at UI Health Care Holden Comprehensive Cancer Center has led a clinical trial researching immunotherapies that could work for that half. A study was recently published in the Journal of Clinical Oncology and has gained attention in the oncology community for finding a 33.6% overall response rate for enrolled patients, in a setting where there were no options.

Turning tumors against themselves

The treatment being studied, called “RP1”, uses a new approach to stimulate the immune system with a virus injected into tumors directly. In this case, it is herpes simplex virus, which has been genetically engineered not to produce herpes, but to have the ability to replicate within the tumor, breaking apart the tumor cells while expressing a protein that acts as a beacon for immune cells. Essentially, it turns the cancer into its own enemy by attacking it from within, then signaling for immune reinforcements. When the immune system identifies the tumor, combined with nivolumab, the “checkpoint inhibitor” drug, it mounts a systemic attack. Checkpoint inhibitors help the immune system to kill cancer cells by making it more difficult for cancer cells to avoid the immune system.

“It opens a huge research door into treating tumors when we put a needle into the tumor and use cells to do the job of shrinking it. Those cells do a better job of treating the tumor than any drug could, because they know exactly what they are looking for. Our immune system knows how to effectively kill something; this treatment just helps it recognize the cancer it needs to kill,” Milhem says.

Another advantage of this type of immunotherapy is how quickly it appears to work for melanoma patients. Patients generally receive the injectable every two weeks, for about six to eight treatments in total. In fact, some patients have actually experienced feeling their tumors shrink while undergoing treatment.

One of those patients is Erin Pazour.

“Let’s find something that works.”

After initially being diagnosed with melanoma by her primary care provider, Pazour was eventually referred to UI Health Care, where it was discovered that her melanoma had spread to a lymph node. Milhem and Pazour decided not to remove the lymph node immediately, so that it could be used as a marker for success of the treatment. However, over time it continued to grow, and Milhem presented Pazour with the option of joining this clinical trial. Pazour agreed immediately.

“I felt like if what we were doing wasn’t working, let’s move on to the next step. Let’s find something that works,” Pazour says.

Every two weeks for four months, Pazour would receive a treatment of the nivolumab infusion, followed by the RP1 injection into her lymph node. At about the halfway point, a CT scan indicated the tumor may have grown slightly. They increased her dose, and within two weeks, she knew it was working.

“I could literally feel the lymph node tumor was getting smaller,” Pazour says.

After eight treatments, she was biopsied again and it was determined there was nothing left of the tumor. Her lymph node was subsequently removed. Initially she would visit Milhem every three months for checkups; for the next five years, she will have checkups every six months for CT scans.

“At this point, I am considered cancer free,” Pazour says.

Linda Jacobs is another participant in this clinical trial with angiosarcoma, who has been cancer-free for more than two years.

Iowa is leading the way.

Though it is a nationwide study, Iowa has the distinction of enrolling the greatest number of participants. Of the 353 melanoma and sarcoma patients who received the drug, 51 were treated at Iowa.

Milhem is also quick to point out that these trials take a lot of work, and he isn’t running it alone. Teena Davis-Van Daele, clinical trials coordinator is the coordinator for the trial and handles many of the behind-the-scenes logistics and recordkeeping required for a study like this. He also mentions advanced practice practitioner Michele Freesmeier, physician assistant, hematology/oncology, as instrumental in caring for many of the trial patients. These are just few of many who make these trials run smoothly.

“We have built a fantastic team here at UI Health Care and being on the forefront of these cancer treatments really shows what we are capable of,” says Milhem.

Though the treatment has not yet received FDA approval, the results to date are compelling and it is being watched closely by oncologists with the hopes that it will soon be available for other patients as a standard treatment.