Amgen posts early clinical data on closely watched KRAS drug

SVB Leerink analysts called the non-small cell lung cancer response rate “encouraging.” (Amgen)

Amgen has posted early clinical data on its effort to drug key oncogene KRAS. The readout reveals early signs of efficacy, with one-third of the heavily pretreated lung cancer patients enrolled in the trial having partial responses.

The prevalence of KRAS mutations in human tumors and perception that it is undruggable have made the oncogene a notorious target. Around one-quarter of all human tumors have KRAS mutations, and about 14% of lung adenocarcinomas have the G12C mutation. Yet, the lack of obvious binding sites on the KRAS protein have left drug developers unable to seize the opportunity those numbers show.

AMG 510 has emerged as one of the most closely watched early-phase assets in the industry because it may enable Amgen to start to realize the KRAS opportunity. Now, Amgen has shared an early look at data on the drug.

Amgen enrolled 22 late-stage cancer patients with G12C mutations in the KRAS gene and treated them with AMG 510, leading to the release of an abstract ahead of the upcoming American Society of Clinical Oncology (ASCO) annual meeting. 

Of the 10 patients with six weeks of follow-up, two had partial responses and six had stable disease. Writing in a note to investors, analysts at SVB Leerink said the results “appear less impressive than expected” at first glance, particularly as they come from a genetically pre-qualified patient cohort. But the complexion of the results changes when the data are broken down by disease.

Six of the evaluable patients had non-small cell lung cancer (NSCLC). In this population, Amgen saw two partial responses and two cases of stable disease, resulting in response and clinical benefit rates of 33% and 66%, respectively. The results in the four colorectal cancer patients were far less impressive. 

Calling the NSCLC response rate “encouraging,” the Leerink analysts predicted the divergent results will drive Amgen to prioritize lung cancer as it plots out the next steps in the development program.

“The rate of responses among the lung cancer cohort … suggests that Amgen will embark on the cohort expansion in this cohort. The response rate in all these populations is likely to improve from this initial report, and is certainly better in NSCLC than would be expected from either chemotherapy or a PD-1 antibody alone in such refractory patients,” the analysts wrote.

In the longer term, the future of AMG 510 may be in combinations. Amgen outlined plans to test the G12C inhibitor in combination with an anti-PD-1 checkpoint inhibitor late last month. Observers have also noted the potential to pair it with drugs aimed at targets including SHP-2 and mTOR.

As Amgen works to seize those opportunities, it may face competition from Mirati Therapeutics, a biotech with a rival drug aimed at KRAS G12C mutation-positive cancers in early-phase development. 

The next step in the race will come at ASCO, when Amgen will share updated data that may shed more light on the potential efficacy of AMG 510 as a monotherapy. Most of the patients who were enrolled but not evaluable as of the ASCO abstract cutoff had colorectal cancer.