image: Susanna Ulahannan, M.D., is an oncologist at the University of Oklahoma Health Stephenson Cancer Center.
Credit: University of Oklahoma
OKLAHOMA CITY – The U.S. Food and Drug Administration has granted Fast Track Designation to a new drug combination for metastatic colorectal cancer, following encouraging results from a clinical trial led in part by the University of Oklahoma Health Stephenson Cancer Center. The treatment offers potential hope for patients whose tumors lack a key DNA repair protein called ATM.
The drug combination pairs alnodesertib, a targeted therapy that blocks cancer cells’ ability to repair DNA damage, and a low dose of irinotecan, a chemotherapy drug that causes that damage. Together, the drugs exploit a weakness in cancer cells that are already deficient in the ATM protein.
In the trial, a substantial number of patients with ATM-deficient tumors who received the treatment experienced reductions in the size of their cancers.
“We consider this a triple hit because we target the cancer in three different ways. We target the right tumor (those with ATM deficiency) and then we attack it with two treatments that work synergistically, one that damages the DNA and the other that prevents the cancer cell from repairing the DNA and surviviving,” said Susanna Ulahannan, M.D., OU Health oncologist and associate professor in the OU College of Medicine, who was the national principal investigator for the cohort of colorectal cancer patients. “The treatment responses we have seen are very exciting, and they are in a patient group that has very few options.”
Like other forms of chemotherapy, irinotecan damages the DNA of cancer cells. Normally, a protein called ATR would try to repair that damage before the cells divide again. But alnodesertib, an ATR inhibitor, blocks the repair signal, preventing cancer cells from recovering and multiplying. This mechanism is particularly effective in cancers that already have defective repair systems, such as those lacking ATM.
The drug combination’s Fast Track Designation is for patients who have already received at least two rounds of other colorectal cancer treatments that have not been effective. Alnodesertib is from Artios Pharma Limited and was tested in the STELLA clinical trial.
According to the American Cancer Society, more than 154,000 people will be diagnosed with colorectal cancer in 2025, and 52,000 people are expected to die from the disease. The lifetime risk of developing colorectal cancer is 1 in 24 for men and 1 in 26 for women.
“We have had only two good treatment options for metastatic colorectal cancer, so there is a very high unmet need. While colorectal cancer overall is declining, it is increasing in people under 50. We are seeing young, otherwise healthy patients who have limited treatment options. This clinical trial has produced very promising results,” Ulahannan said.
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About the University of Oklahoma
Founded in 1890, the University of Oklahoma is a public research university with campuses in Norman, Oklahoma City and Tulsa. As the state’s flagship university, OU serves the educational, cultural, economic and health care needs of the state, region and nation. In Oklahoma City, the OU Health Campus is one of the nation’s few academic health centers with seven health profession colleges located on the same campus. The OU Health Campus serves approximately 4,000 students in more than 70 undergraduate and graduate degree programs spanning Oklahoma City and Tulsa and is the leading research institution in Oklahoma. For more information about the OU Health Campus, visit www.ouhsc.edu.
Method of Research
Randomized controlled/clinical trial
Subject of Research
People