Amgen offers hope in KRAS-mutated cancer with sotorasib read-out

Last year Amgen intrigued scientists and investors alike after announcing data showing it had produced the first drug that seemed to work against KRAS mutations, which are found in lung and other cancers but have proved hard to treat.

At this year’s European Society for Medical Oncology (ESMO) conference, Amgen announced updated data from the full phase 1 cohort of the CodeBreak 100 study.

This tested the newly-named sotorasib, previously known by the codename AMG 510, across several types of solid tumour.

Data simultaneously published in the New England Journal of Medicine from 59 patients with non-small cell lung cancer (NSCLC) was highlighted during an oral presentation at ESMO.

Sotorasib demonstrated confirmed objective response rate (ORR) and disease control rates (DCR) of 35.3% and 91.2%, respectively, in 34 heavily pretreated patients (median of two prior lines of therapy) with NSCLC, who were treated with the 960 mg daily dose (data cutoff of June 1, 2020).

Anticancer activity was seen across all dose levels in patients with NSCLC, with a confirmed ORR of 32.2% and DCR of 88.1%, and median duration of response of 10.9 months, with 10 of 19 responders still in response as of the data cutoff.

Tumour shrinkage was observed in 71.2% of patients at the first week-6 assessment. Median progression-free survival (mPFS) in patients treated with sotorasib was 6.3 months.

Safety and tolerability in patients with NSCLC were consistent with previously seen CodeBreaK 100 results.

No dose-limiting toxicities were observed and there were no fatal treatment-related adverse events (TRAEs). The most common TRAE was diarrhoea, occurring in around a quarter of patients.

Professor Fabrice Barlesi, medical director of Gustave Roussy Institute, Paris, France commented “There are currently no approved targeted therapy options for KRAS G12C and patients remain in need of additional treatment options, which makes these new findings particularly important.”

It’s still early days for sotorasib, but the consensus of opinion from the virtual conference was that sotorasib could be a breakthrough in the treatment of KRAS-positive cancers.


Amgen’s data sparked several large deals with KRAS-developing biotechs, with Merck & Co and Boehringer Ingelheim two of the highest profile examples.

Expect to see more activity in KRAS if Amgen and its competitors produce more supportive data.


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