In Amgen’s battle with Mirati Therapeutics to develop the best KRAS inhibitor, the biotech giant may have reached the FDA finish line first. But Mirati's rival drug seems to carry clinical advantages of its own.
While Amgen won a highly touted approval last May for Lumakras as a treatment for non-small cell lung cancer, Mirati's adagrasib is showing strong potential in the clinic as the company gears up for an FDA review.
The theme continued this week with Amgen’s presentation Tuesday at the American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium. In an early-stage trial of 38 with advanced pancreatic cancer, Lumakras shrunk tumors in 21% patients. In addition, patients on the drug were alive without disease progression at a median of 4 months and remained alive at a median of 6.9 months.
While calling the results “encouraging and clinically meaningful,” Amgen said it would expand the trial, dubbed CodeBreak 100, to more patients with pancreatic and other tumor types.
But the results stand in contrast to those Mirati revealed last month. In the Krystal-1 study of 27 patients with cancers of the biliary tract, adegrasib shrunk tumors in 50% of those with pancreatic cancer and a 35% of those with other gastrointestinal cancers. Patients with pancreatic cancer were alive without progression of their disease for a median of 6.6 months, while the median duration was 7.9 months for those with GI tumors.
It's still early to draw conclusions from trials involving small numbers of patients, and cross-trial comparisons always come with caveats.
Still, Amgen says the Lumakras results are encouraging considering the current FDA-approved second-line therapy in this type of pancreatic cancer comes with a median survival duration of six months and a 16% rate in shrinking tumors. Additionally, after first- and second-line chemotherapy, no treatments have demonstrated a survival benefit, a spokesperson said.
“We cannot make cross-trial comparisons,” an Amgen spokesman wrote in an email. “(But) data show encouraging and clinical meaningful anticancer activity and a positive benefit/risk profile.”
Meanwhile, in colorectal cancer, Mirati has demonstrated the potential of adagrasib—also in early-stage testing and in a small number of patients. While adagrasib shrunk tumors in 22% of patients, Lumakras produced a 9.7% figure, prompting Amgen to drop the drug as a CRC monotherapy.
Mirati is anticipating FDA approval of adagrasib this year as a monotherapy in second-line lung cancer. The company said it submitted the drug to the agency in December.
For its part, Amgen will pursue Lumakras for the treatment of pancreatic cancer—one of the toughest cancers to solve and where the five-year survival rate is only 10%.
“After decades of research, current treatments for patients with pancreatic cancer provide limited survival benefit, illustrating the critical need for novel, safe and effective treatment options,” John Strickler, M.D., a gastrointestinal oncologist at Duke University School of Medicine, said in Amgen’s release.