Pathologist Erika Hissong (L) and Oncologist Pashtoon Kasi (R) were two of the scientists involved in a new study demonstrating efficacy of a new immunotherapy against colorectal cancer.
Weill-Cornell Medicine
A combination immunotherapy developed by biotech company Agenus administered before surgery destroyed over 80% of a tumor before it was removed.
Colorectal cancer is one of the most diagnosed cancers in the United States. The American Cancer Society estimates there will be over 150,000 new cases diagnosed, and that over 52,000 Amerricans will die from the disease this year. Although it can be treatable if caught early, advanced cases of the cancer, especially if it spreads to other parts of the body, are much more likely to be fatal.
In recent years, advances in cancer treatment have come from a class of drugs called immunotherapies, which help harness the body’s own immune system to fight cancer. One challenge in treating colorectal cancer is that for the vast majority of patients, immunotherapies have largely proven ineffective. However, a new report published in the journal Oncogene Thursday found that in a small scale study, patients treated with an experimental immunotherapy prior to having their tumors surgically removed saw about 80% to 90% of the cancer cells killed in a manner that suggests it’s less likely that the cancer will return.
“Within weeks, it was like it had shriveled down to nothing,” Pashtoon Kasi, director of colon cancer research at Weill Cornell Medicine and lead author of the study, told Forbes.
In the study, 12 patients with advanced colon and rectal cancers that hadn’t yet spread to other parts of the body were treated with a combination of two immunotherapies discovered and being developed by Massachusetts-based biotech company Agenus: botensilimab and balstilimab. These drugs target different ways in which tumors “hide” from the immune system, enabling the body to attack these tumors. The treatment took place a few weeks prior to a surgical removal of their cancers. Because these types of treatments create an inflammatory response, which can increase the risk of infection from the surgery, only half of a typical dose was given, Kasi said.
After the surgery, the tumors were then examined by study author Erika Hissong, a pathologist at Weill Cornell Medicine. The paper only presents two of the patient results so far, but both showed similar results: an “inside-out” response where the tumor cells were invaded by inflammatory immune cells, which targeted the disease.
In fact, most of the tumors that were surgically removed and examined were “actually comprised of this inflammation and reactive changes in the tissue as the tumor is being wiped out by the immune system, rather than containing viable tumor cells,” Hissong told Forbes in an email.
She also noted that her findings showed that the tumor is being “pushed out” of the patient’s bowel wall, as opposed to other types of cancer treatments that might attack a tumor from its surface as opposed to its source tissue. That suggests it’s more likely that a successful surgery means the cancer won’t come back.
Figure illustrating the action of the combination immunotherapy.
Weill-Cornell Medicine
What’s noteworthy about this result is that the patients here, like about 85% of colorectal cancer patients, have what are called “mismatch repair proficient” cancers, which produce highly mutated tumor cells that typically do not respond to immunotherapy. What’s more, Kasi added that based on the results, it may be possible to reduce or even eliminate the need for chemotherapy after surgery, which would otherwise be standard in these kinds of cases.
To be sure, this paper has some limitations. For one, it only reports on two of the 12 patients who received treatment earliest in the study. It also didn’t show any comparisons to other types of treatments with this type of patient and setting. That said, Kasi said the full results for all twelve patients should be available in the coming months and that his team is also planning future trials with more comprehensive analyses. However, he noted that these results were published because of how effective the drug seemed to be in these preliminary results. “It was not just the kill but how we analyzed the mechanisms of action of the kill,” he said.
This isn’t the only study with this immunotherapy combination that’s shown results in colorectal cancer, either. In January, results from a phase 1 clinical trial found that for patients with metastatic colorectal cancer, the treatment nearly tripled one year survival rates. In June, the Agenus reported that patients were surviving for several months longer than the traditional standard of care with durable responses.
In April, the FDA granted fast track designation for the treatment combination, which helps speed the approval process in medical areas where there’s a large unmet need. Larger clinical studies of the therapy are also underway. In August, Agenus announced that it was putting the rest of its clinical pipeline on hold to pursue commercialization of the botensilimab/balstilimab combination.
“The observed clinical benefit in solid tumors underscores the program’s game-changing potential,” Agenus CEO Garo Armen said in a statement. “And our rapid progress towards a first filing in 2024 highlights the necessity for prioritization in every aspect of our operations.”