A phase 2 study of sotorasib in advanced KRAS p.G12C mutated non-small cell lung cancer has delivered promising results including a disease control rate of 80.6%.
Dr Bob Li, from the Memorial Sloan Kettering Cancer Centre in the US, presented the results of CodeBreak 100 at the recent IASLC 2020 World Lung Cancer Conference.
The findings build on phase 1 results reported in the limbic last year and support the FDA’s December 2020 approval of “breakthrough therapy designation” to sotorasib for the treatment of patients with locally advanced or metastatic NSCLC with the KRAS G12C mutation.
The study enrolled 126 NSCLC patients with a confirmed KRAS p.G12C mutation who had received up to three prior lines of treatment and experienced disease progression. Enrolled patients were treated with the once daily oral therapy and were followed for a median period of 12.2 months.
The study found an objective response rate of 37.1% with a median time to objective response of 1.4 months and median duration of response of 10 months. The median PFS was 6.8 months with 43% of responders remaining on treatment without progression.
Dr Li said sotorasib was well tolerated with treatment-related adverse events leading to discontinuation in only 7.1% of patients.
The most commonly reported grade 3 AEs were increases in aminotransferase levels and diarrhoea. There were no treatment-related deaths.
Dr Li, who is also MSK’s Physician Ambassador to China and the Asia-Pacific, said the tumour response to sotorasib was observed across a range of biomarker subgroups including patients with negative or low PD-L1 expression and those with mutant STKL11.
“This is a historic milestone in [lung] cancer therapy. After four decades of scientific efforts in targeting KRAS, sotorasib has potential to be the first targeted treatment option for this patient population with a high unmet need,” he told the meeting.
CodeBreak 200, a phase 3 trial comparing sotorasib with docetaxel is currently recruiting internationally including at Australian sites.