A first-of-its-kind drug developed by Amgen shrank tumors in a little over a third of lung cancer patients enrolled into a mid-sized study, affirming promising results from an earlier trial that had excited oncologists and made the medicine one of the most closely watched in biotech.
The drug, called sotorasib, is aimed at tumors that have been driven to growth by mutations in a gene called KRAS. Most common in lung, colon and pancreatic cancers, KRAS mutations have defeated scientists' best efforts to design targeted treatments for more than 30 years.
Sotorasib is the first drug found to work against a particular type of KRAS mutation known as G12C, thought to be present in about 13% of diagnosed non-small cell lung cancers. Amgen's breakthrough built on work done by researchers at the University of California, San Francisco, who found a "hidden groove" on the mutant KRAS protein that drugs could be designed to bind to.
Data released by Amgen on Thursday show 46, or 37%, of 124 participants in the company's Phase 2 study responded to treatment. Three patients' cancers disappeared entirely. Importantly, those responses also appeared durable, lasting for a median of 10 months. The median time to disease progression or death, a standard interim measure of a cancer drug's benefit, was nearly seven months.
The results are similar to what Amgen reported from the smaller Phase 1 trial, which included 59 patients with lung cancer.
For the treatment of KRAS-mutated lung cancer, the finding marks a significant advance. Nearly all the patients in the study had received prior treatment with either chemotherapy or with immunotherapy drugs like Merck & Co.'s Keytruda, and seen their cancer progress. Eighty percent had received both.
Once those options are exhausted, there are no targeted drugs to choose from and the response rates to another round of chemotherapy are typically poor. The 6.8 months recorded for progression-free survival by investigators in Amgen's study is similarly about twice what would be expected with chemo.
A majority of participants in the study experienced some side effects to treatment, typically diarrhea, nausea and elevations in liver enzymes. In 20% of patients, side effects were more severe, and 7% discontinued treatment. That latter number is much lower than what would be expected for chemotherapy, according to Greg Friberg, a therapeutic area head at Amgen.
There were no deaths associated with sotorasib.
Data from the study were unexpectedly released one day ahead of schedule, and will be presented Friday at the World Conference on Lung Cancer. Amgen, which announced the study succeeded last October, had withheld its findings to time with the conference.
While sotorasib is effective in some, the majority of patients in the study still did not respond to treatment, suggesting their tumors may rely on other mutations in addition to KRAS to fuel their growth.
"The switchboard that goes through KRAS is important but there are going to be other levers at play," said Friberg, in an interview.
The biotech is currently studying sotorasib in combination with several other types of cancer drugs, including immunotherapy. A Phase 3 trial comparing sotorasib directly to chemotherapy is recruiting volunteers and Amgen hopes to complete enrollment this year.
Sotorasib's development is the fastest Amgen's ever accomplished for an experimental drug, with just over two years passing between the first patient treated and the company's initial filing with the Food and Drug Administration for an approval.
Over that time, sotorasib has become the most important medicine in Amgen's pipeline and a key piece of the drugmaker's plans to build up a cancer business.
On Thursday, Amgen disclosed it has completed submissions to regulators in the U.S., U.K., EU, Australia, Brazil and Canada. Should the drug win approval, the company, and the analysts that watch it, expects fast sales, although the COVID-19 pandemic could make reaching doctors more difficult.
While Amgen is the first to reach regulators with a KRAS-blocking drug, other companies are following close behind, having capitalized on the research that laid out an approach to designing targeted treatments.
One of the most advanced is Mirati Therapeutics, a small biotech that's developing a drug called adagrasib. Results from an early study showed the treatment can shrink tumors in patients with relapsed lung cancer.
Johnson & Johnson, Boehringer Ingelheim and, most recently, Roche, are also testing KRAS inhibitors.
Editor's note: This story has been updated with additional detail throughout.