The FDA approved Amgen’s Lumakras (sotorasib) last week, the first drug targeting KRAS-mutated cancer to get the agency’s OK. But the clinical and commercial future of the drug is uncertain.
On the heels of last week’s accelerated approval of Lumakras (sotorasib) by the FDA, researchers presented results today from the phase 2 trial that led to drug’s approval at the annual meeting of the American Society of Clinical Oncology.
“I believe that based on the results, sotorasib represents the new standard of care for patients with KRAS G12C-mutated nonsmall cell lung cancer that have failed at least one prior line of systematic therapy,” said the lead investigator Ferdinandos Skoulidis, M.D.,Ph.D., of the M.D. Anderson Cancer Center in Houston, in an interview with Managed Healthcare Executive.®
Lumakras targets mutated versions of the KRAS (usually pronounced K-ras) gene, which
researchers have identified as being instrumental in the development of cancer but have been an elusive, possibly “undruggable” target for treatment for decades. Skoulidis explained that the gene has a “smooth and featureless surface” that make it difficult for treatment drugs to latch on to.
About 1 in 8, or 13%, of patients with nonsquamous nonsmall cell lung cancer have tumors with the KRAS G12C-mutated genes that Lumakras targets, according to Skoulidis. He said each year roughly 13,000 patients in the U.S. will be eligible to take the drug based on its current indications. Lumakras is taken as a daily pill.
Lumakras, which was developed by Amgen, has the history-making distinction of being the first FDA-approved that targets the KRAS gene, but the clinical and commercial fate of the drug is not certain. A phase 3 trial called CodeBreak200 that is comparing the new drug to docetaxel, an established cancer drug, is underway. Skoulidis said results from previous results suggest that Lumakras is more effective but such comparisons have to be interpreted with caution and are not as valid as head-to-comparisons. Lumakras may also face competition: Mirati Therapeutics, a San Diego biotech company, reported positive results for adagrasib, its KRAS G12C inhibitor, at a European lung cancer meeting earlier this year. There’s also a second generation of KRAS-targeted drugs at various stages of development that could overshadow Lumakras, despite its first-out-of-the-gate status.
Cost issues could be another hurdle. Media reports last week said Amgen was planning to price the drug at $17,900 a month, a price that payers may balk at depending on how the drug stacks up against its alternatives.
Amgen included many of the results of the phase 2 trial, called CodeBreak100, in its announcement last week about the FDA approval so results presented today and published simultaneously in the New England Journal of Medicine were somewhat anticlimactic. They showed that 46 of the 124 patients (37%) of the patients included in the analysis had an objective response to the Lumakras and median duration of the response was 11.1 months. The patients had median progression-free survival of 6.8 months and a median overall survival of 12.5 months. Most (69.8%) patients experienced treatment-related adverse events but they were serious in a smaller group (20.6%).
Skoulidis said one of the most important findings from the phase 2 trial may be response seen in patients with a co-occurring mutation in the STK11 gene and unmutated KEAP1 gene.
“Sotorasib only works in patient with KRAS G12C-mutated nonsmall cell lung cancer but it appears, based on this data, that there is a signal that it might work better in KRAS G12C-mutated nonsmall cell lung cancer that harbor a co-mutation in STK11, particularly when KEAP1 … is wild type,” he said in the interview with MHE.
If the finding is confirmed in larger trials, it might point to a subgroup of patients who particularly benefit from Amgen’s KRAS-targeted drug and perhaps to its use as a first-line drug, Skoulidis said.
Only 2 of 126 patients in the phase 2 trial were Black. Skoulidis said both Amgen and the participating academic institutions are aiming to improve of underserved and underrepresented patient populations in the follow-up phase 3 trial. He also he hopes that the approval of Lumakras will “galvanize and activate efforts to routinely obtain comprehensively genetic profiling of basically any patient with locally advanced or metastatic nonsmall cell lung cancer.”