On September 27, Amgen presented the latest data from the Phase I study of AMG 510 in patients with KRAS G12C-mutated solid tumors at the ESMO 2019 Congress. This open-label, multicenter, Phase I study enrolled patients with KRAS G12C-mutated solid tumors who had received two or more prior lines of therapy. The study design included four dose cohorts (180 mg, 360 mg, 720 mg, and 960 mg), administered orally once daily. The primary endpoint was to evaluate the safety of AMG 510, while secondary endpoints included pharmacokinetics, objective response rate (ORR; assessed every 6 weeks), duration of response, and progression-free survival (PFS).
AMG 510 is the first oral, selective, reversible inhibitor targeting KRAS G12C. The results of the aforementioned Phase I study were previously presented at this year’s ASCO and WCLC conferences. At the ESMO 2019 Congress, the antitumor activity of AMG 510 in the treatment of colorectal cancer (CRC) and appendiceal cancer was disclosed for the first time, and updated findings on non-small cell lung cancer (NSCLC) were also reported. The data further demonstrated that AMG 510 was well tolerated, with no dose-limiting toxicities observed.
This study enrolled 76 patients with KRAS G12C-mutant solid tumors. As of July 2019, among the 55 patients evaluable for efficacy, there were 29 patients with colorectal cancer (CRC). Of these, 12 CRC patients received AMG510 at a daily dose of 960 mg; results showed that one patient achieved a partial response and ten patients achieved stable disease, yielding a disease control rate of 92%. Currently, ten patients remain on treatment. Among the 13 patients with non-small cell lung cancer (NSCLC) who received AMG510 at a daily dose of 960 mg, seven achieved a partial response and six achieved stable disease, resulting in a disease control rate of 100%. Of the two patients with appendiceal cancer, one achieved a partial response and one achieved stable disease.
RAS was the first oncogene identified in human tumors and remains one of the most prevalent oncogenic mutation genes, with over 30 years having passed since its discovery. The RAS gene family currently includes three known members: KRAS, NRAS, and HRAS, among which KRAS mutations are the most common, accounting for approximately 85%. KRAS G12C mutations account for approximately 13% of non-small cell lung cancer (NSCLC) cases, 3%–5% of colorectal cancer cases, and 1%–2% of other solid tumors. In the United States, approximately 30,000 new patients are diagnosed annually with cancers harboring KRAS G12C mutations.