Sotorasib, a cancer drug developed by Amgen aimed at blocking the KRAS G12C mutation, reduced tumors in 37% of patients with advanced lung cancer and delayed tumor progression by about seven months, according to new clinical data—findings that, according to some experts, represent a significant breakthrough for oncology care, STAT News' Adam Feuerstein reports.
About the KRAS G12C mutation
According to Feuerstein, the KRAS protein has long been known to cause cancer, but scientists have struggled to develop drugs to block it because the protein has virtually no features and is spherical, meaning that there are few points where drugs can attach to the protein. Bob Li, an oncologist and lung cancer expert at Memorial Sloan Kettering Cancer Center and the principal investigator on Amgen's clinical trial, told Feuerstein that "KRAS is the most frequent genetic driver of human cancer," and "[d]espite 40 years of hard research, we have not been able to crack it."
Although there are some approved cancer drugs that target the KRAS protein, there currently is no approved treatment that directly targets the G12C mutation of the KRAS protein, Feuerstein reports. According to Amgen, the G12C mutation of the KRAS protein is found in about 14% of non-small cell lung cancer adenocarcinomas, as well as 4% of colorectal cancers and 2% of pancreatic cancers.
Amgen touts clinical trial data on sotorasib as promising
But Amgen on Thursday announced the new results from its Phase 2 trial on sotorasib, which showed promise against the G12C mutation, the company said.
For the trial, Amgen enrolled 126 patients who had advanced non-small cell lung cancer with the genetic mutation KRAS G12C. All of the patients previously had been treated with a median of two other anti-cancer medicines that were no longer working. There was no control group in the trial, so all of the participants received sotorasib.
In total, 37% of the 124 evaluable patients in the trial saw a reduction in tumor size that was clinically meaningful after their treatment with sotorasib, Amgen said. Further, Amgen said that three patients' tumors were completely eliminated. The median amount of time for tumor response was 10 months, according to Amgen.
Further, the data showed that the median time of progression-free survival, or the amount of time patients lived before their tumors worsened, was 6.8 months among all 126 patients enrolled in the trial, Amgen said.
About 20% of patients reported side effects during the trial, and nine patients stopped their treatment with sotorasib during the trial because of side effects. One patient experienced severe toxicity of lung inflammation and difficulty breathing, Amgen said. No deaths occurred as a result of side effects related to sotorasib, however.
'This is a clear winner'
Li said the clinical trial results represent "a milestone in oncology," given the difficulties researchers have had in targeting the KRAS protein. Further, Li said the nearly seven-month-long delay in tumor progression observed in the trial was double what physicians typically see with standard chemotherapy treatments.
"This is to me a significant step forward for these patients," he said.
Separately, Narjust Duma, an oncologist and lung cancer expert at the University of Wisconsin School of Medicine and Public Health, called the results "a big deal … because KRAS is a holy grail of lung cancer."
According to Duma, sotorasib could make it possible for physicians to treat a large number of lung cancer patients whose prognosis is poor otherwise.
Similarly, Stephen Liu, director of the lung cancer program at Georgetown Lombardi Comprehensive Cancer Center, said, "This is a clear winner for second-line lung cancer"—meaning the treatment could be useful for treating patients for whom first-line cancer treatments stop working, Feuerstein reports.
However, Liu said he's not as confident about using sotorasib as a first-line treatment for patients recently diagnosed with lung cancer. "For a targeted drug, you want to see a majority of patients have a response, so a 37% response rate doesn't cut it," he said.
Still, Liu added that providers could use sotorasib in combination with another treatment, such as a checkpoint inhibitor, to be more effective for first-line lung cancer patients (Feuerstein, STAT+, 1/28 [subscription required]).