Sotorasib licensed in non-small-cell lung cancer patients with G12C KRAS mutations

July 2021 Pharma News Tobias Rawson

On May 28th, The FDA approved the KRAS inhibitor sotorasib for use in patients with non-small-cell lung cancer (NSCLC), whose tumour harbours a mutation called G12C in the KRAS gene, and who have already received at least one previous therapy regimen. Over 200,000 new cases of NSCLC are diagnosed every year in the United States, with approximately 13% oh these cases harbouring the G12C mutation. The approval follows the results of a global phase II trial, which found sotorasib reduces tumour size and improves survival outcomes in this subset of NSCLC patients.

Speaking from Washington Univeristy, Dr Ramaswamy Govindan, MD, said “This is a group of patients whose tumours have been difficult to treat and for whom we did not have targeted therapies. The new drug is addressing an unmet need for these patients, targeting the most common mutation that we can go after. We’re also continuing to investigate this drug in combination with other experimental drugs to see if we can further improve responses and survival.”

Complete response observed in 34% of patients

Enrolling 126 NSCLC patients with a G12C mutation to receive a once daily tablet of sotorasib, 82% of patients experienced at least some form of tumour shrinkage. Furthermore, 37% of patients experienced a reduction in size by at least 30%. Overall, 34% of patients experienced a partial response, with 3% of patients achieving a complete response. On average, tumour shrinkage was approximately 60% throughout all responders. Sotorasib was also able to demonstrate a clinically meaningful increase in progression-free survival of approximately 7 months. In contrast, the progression-free survival with current standard therapy in this subset of patients is usually 2-4 months.

KRAS gene alterations have long been considered not amenable for targeted therapies. This highlights work that Washington University has excelled at over the past few decades — studying the genomic alterations in tumors with the goal of identifying treatment targets. This early cancer genome research is now coming full circle to help our patients,” said Govidan.

However, 7% of patients did have to stop sotorasib due to adverse events, although these were not life-threatening and no patients died as a result of treatment. A further 22% of patients had to receive a reduced dose of sotorasib due to treatment-emergent adverse events. Overall, 70% of patients experienced side effects, with the most common being diarrohea, fatigue, nausea and increased liver enzymes.

“Sotorasib showed clinically significant benefit without any new safety concerns in patients with this specific form of KRAS mutant lung cancer,” Govindan said. “Moving forward, our team will seek to inform the development of combination therapies featuring sotorasib and other emerging drugs, and to determine which best fit the mix of mutations in each patient’s cancer cells.”  

A phase 3 clinical trial investigating the efficacy of sotorasib in this patient group versus docetaxel is now underway.


Skoulidis F et al., Sotorasib for lung cancer with KRAS p.G12C mutation. New Eng J Med. 2021; 384: 2371-2381.