Amgen reports the results of AMG 510's first human clinical trial

In this open label phase I study, 35 patients with krasg12c mutation, including 14 patients with non-small cell lung cancer, 19 patients with colorectal cancer, and 2 patients with other types of tumors, who had received at least two lines of treatment before, were divided into four groups according to the dosageAMG 510 was given 180, 360, 720, 960mg once a dayThe primary end point of the study was safety, and the secondary end points included pharmacokinetics, objective response rate (evaluated once every six weeks), response duration, and progression free survival< br / > the results showed that in 10 assessable NSCLC patients, 5 (50%) had partial remission (PR), 4 had stable disease (SD), and the disease control rate reached 90% (9 / 10); 5 patients had been treated for 7.3-27.4 weeks when they read the data, and were still receiving treatmentOne of the patients who got PR continued to improve after reading the data and got complete remission (CR) at the 18th week< br / > in a total of 18 evaluable colorectal cancer patients, 13 patients achieved SD, and most of them received 180 mg or 360 mg dose level drugsSo far, 26 patients are still receiving treatment, and 9 patients have terminated treatment< br / > in terms of safety, no dose limiting toxicity of AMG 510 was found at the four dose levels tested in the phase I studyThe main adverse events related to AMG 510 treatment were mild grade 1, with the incidence of 68%There were 2 grade 3 treatment-related adverse events, including anemia and diarrheaNo serious treatment-related adverse events above level 4 were found< br / > according to David MReese, executive vice president and R & D director of Amgen, KRAS is the first carcinogenic gene found in human body more than 30 years ago, and has become one of the most active research directions in cancer research since thenHowever, due to the lack of small molecule binding pocket in the traditional sense of this protein target, it is still considered as "not a drug"AMG 510 works by binding to the hidden grooves on the surface of KRAS protein, which can irreversibly bind to the cysteine on the mutated KRAS protein, thus making KRAS enter into the inactivated stateBecause of its high selectivity for krasg12c, we believe that AMG 510 has a great potential for drug preparation, which can be used in a single drug, or in combination with other targeted drugs and immunotherapy" < br / > ras gene family is the human carcinogenic gene with the highest mutation probability, among which KRAS mutation is the most popular KRAS mutations are more common in solid tumors The prevalence of krasg12c mutations at specific sites was about 13% in NSCLC, 3% - 5% in colorectal cancer and 1% - 2% in other solid tumors < br / > the mutation probability of ras gene in common human cancers < br / > there are about 30000 newly diagnosed patients with krasg12c mutation in the United States every year AMG 510 is the first krasg12c candidate drug to enter the clinic after 30 years of studying Ras pathway, and has obtained the orphan drug qualification granted by FDA for treating krasg12c mutation positive NSCLC and colorectal cancer < br / > original title: asco2019 𞓜 30 years long, KRAS inhibitor ushers in the dawn