HonorHealth Research Institute is part of an international effort to create one of the first immunotherapy drug combinations to successfully treat colorectal cancer, the nation’s second leading cause of cancer-related deaths.

An estimated 53,000 Americans will die this year from colorectal cancer, and though generally seen in older adults, it is becoming more frequent among those aged 20 to 50 who are not usually screened for this often aggressive cancer, a press release explained. 

Like all cancers, early detection leads to more successful patient outcomes.

“This was the first time immunotherapy has really been shown to be working in this most common type of colon cancer,” Dr. Sunil Sharma, chief of translational oncology and drug development at HonorHealth Research Institute, stated in the release.

Dr. Sharma is one of the authors of a three-year study of 148 patients worldwide published June 13 in the journal Nature Medicine.

This study documents the positive effects of a combination treatment of two immunotherapy drugs — botensilimab and balstilimab — on microsatellite stable metastatic colorectal cancer, which is the most common type of colon cancer, and one that has generally not been responsive to immunotherapy.

HonorHealth Research Institute was one of the first of over a dozen major research sites in the study and one with among the highest enrollments, according to the release

“We’ve shown the proof of principle that immunotherapies can work against this disease. This creates a backbone upon which we can hopefully build even better immunotherapies,” Dr. Sharma stated. 

This study sets them up to make more combinations on top of this platform that seems to be working, and hopefully will allow for better results in the future, Sharma continued. This drug combination was well-tolerated by patients in the study.

Dr. Michael S. Gordon, chief medical officer of HonorHealth Research Institute, noted that the Research Institute is focused on working towards earlier diagnosis in this patient population, using more up-to-date screening technologies to forestall this epidemic of cancer. 

Dr. Gordon, who is also the author of the research paper, said that combination immunotherapy can overcome cancer’s attempt to hijack the body’s immune system, according to the release.

The combination of the two antibodies in the therapy sidesteps what are known as immune checkpoint blockades, natural elements that ordinarily prevent immune cells from attacking healthy tissue, but which cancer cells also use to cloak themselves.

“If the immune system gets overly aggressive, it can attack the patient’s own body. But if the immune system is shut down, it can’t fight the cancer,” Dr. Gordon said. 

Gordon explained that with this therapy, patients end up with larger numbers of immune T cells that can attack the cancer.

The study found that the combination immunotherapy was most effective against cancer that had not metastasized, or spread, to the liver, citing this as a possible future target of investigation. Those without liver metastases showed a higher response rate and a prolonged interval of ongoing stable response compared to patients with liver metastases, according to Gordon.

“There is a unique opportunity for further research,” he said.

Alarming incidents among young adults

However, one of Dr. Sharma’s concerns was the surprising number of younger adults who are, for unknown reasons, developing this disease. 

According to the paper, “Alarmingly, from 1995 to 2019, the number of patients under the age of 55 who were diagnosed with CRC (colorectal cancer) in the United States nearly doubled.”

Sharma said that his whole clinic is filled with younger people dying of colon cancer, characterizing it as a real tragedy because of how often these patients present with advanced or metastatic disease. 

“When they present with symptoms, nobody’s thinking they have colon cancer,” Dr. Sharma stated.

He noted that their condition is often misdiagnosed as irritable bowel syndrome, hemorrhoids or something else, and screens such as colonoscopies usually aren’t recommended until patients are older than 45.

“They get treated late and so it becomes a very aggressive tumor. It’s a real problem,” said Dr. Sharma. “We may need even more aggressive treatment.”

Agenus, the sponsor of the clinical trial, is planning to seek FDA approval for the combination immunotherapy and has initiated a phase 3 clinical trial.

For more about HonorHealth Research Institute cancer clinical trials, contact 480-323-1305.