Updated Phase I data show Amgen's KRAS inhibitor AMG 510 continues to shrink tumours in about half of NSCLC patients

Amgen announced new data Sunday at the World Conference on Lung Cancer (WCLC) from an ongoing Phase I study evaluating its investigational oral therapy AMG 510 in non-small-cell lung cancer (NSCLC) patients with previously treated KRAS G12C-mutated solid tumours. The company said 54% of 13 evaluable patients experienced a partial response at the target dose of 960 mg, while 46% of patients had stable disease. 

"These new data reinforce the earlier positive response rate we shared at ASCO (American Society of Clinical Oncology) in more NSCLC patients receiving AMG 510," commented Amgen R&D chief David Reese. "If we can expand this and show in a large body of patients that we have response rates on the order of 50% or somewhere near that, that is very clinically relevant and meaningful," he said, but cautioned that it is still "early days" and the company is looking to determine "if some of these responses will deepen over time." 

The latest follow-up in a larger group participants includes a subset of 34 NSCLC patients, and 23 of these were evaluable for efficacy. Amgen explained that 13 of the evaluable patients received the target dose of 960 mg once daily, with seven achieving a partial response at one or more time points based on their first imaging scans post-treatment, while the remaining six achieved stable disease, "for a disease control rate of 100%," the company said. Two of the partial responders have died and another left the study due to cancer progression, while one patient with stable disease also died, according to the results. 

"About 50% of the patients seem to be having responses, and that number seems to be durable," said Greg Friberg, head of oncology at Amgen, adding "we are quite hopeful that these results are going to continue to be consistent over time." 

In regards to safety, Amgen reported that there were no observed dose-limiting toxicities among the 34 NSCLC patients, nor any adverse events leading to discontinuation. Nine patients reported treatment-related adverse events (TRAEs) of grades 1 or 2, and three reported grade 3 TRAEs involving anaemia and diarrhoea, while there were no TRAEs of grade 4 or higher. The company noted that 27 NSCLC patients remain on treatment. 

Amgen also stated that AMG 510 has been fast-tracked by the FDA for previously treated metastatic NSCLC with the KRASG12C mutation. Additional data on AMG 510 will be presented at the European Society for Medical Oncology (ESMO) conference in the coming weeks. 

The latest results are the first in patients for a KRAS inhibitor focused on the G12C mutation, potentially putting Amgen in the lead against companies such as Mirati Therapeutics and Johnson & Johnson, which are developing competing drugs. Reese said Amgen is beginning its next study on AMG 510, which the company may use to seek regulatory approval of the therapy. 

Jefferies analyst Michael Yee has suggested that for such very sick lung-cancer patients, any response rate above 35% would be viewed as an achievement. He added that "the higher the response, the tougher it is" for rivals like Mirati, which has yet to report any data for its KRAS-targeting molecule MRTX849. 

For additional analysis, see ViewPoints: What's all the fuss about KRAS inhibitors?  

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