Until now KRAS-positive lung cancers have been considered ‘undruggable’ but early results with the first targeted therapy have shown promising and durable response rates.
Presented at the World Congress on Lung Cancer 2019 meeting in Barcelona, the phase 1 study results for the novel KRAS G12C Inhibitor AMG 510 showed it was effective and well tolerated by 34 patients with NSCLC.
Efficacy results were available for 23 of the patients, who started treatment within the last year showing that 11 (48%) had a partial response, 11 had stable disease and only one showed progressive disease, giving a disease control rate of 96%.
In the optimum dose of 960mg the partial response rate was 54% and there was a 100% disease control rate, said study lead investigator Professor Ramaswamy Govindan from the Siteman Cancer Center at Washington University School of Medicine, St. Louis .
The responses to AMG 510 were generally seen quite rapidly, within 5-6 weeks, he told the meeting.
In terms of durable responses, 5 of 11 patients with partial responses and 5/11 with stable disease were continuing with therapy at the time of the meeting, with five patients already over six months on treatment.
About a third of patients had treatment-related toxicities, but most were grade 1 and 2. There were three patients with grade 3 adverse events (nausea, anaemia and diarrhoea) but none leading to discontinuation.
“This is clearly a very encouraging set of data and shows this very specifically targeted drug is working the way we expected it to ,” said Professor Govindan.
“For a study that has gone on for just about a year … the activity is quite striking with 54% response rates and early indications that these response rates are quite durable,” he said.
The phase 1 trial – which includes centres in Australia such as The Queen Elizabeth Hospital, South/Australia, the Peter MacCallum Cancer Centre, Melbourne – is continuing and there is also a phase 2 trial enrolment underway as well, he added.
Professor Govindan said the KRASG12C mutation was found in about 12-13% of lung adenocarcinomas and NSCLC and 3% of colorectal cancers, but there are currently no targeted therapies for this mutation. KRAS is a guanine-nucleotide-binding protein that acts as a molecular switch inside cells and links to receptor tyrosine kinase activation to intracellular signalling.