The following article features coverage from the IASLC North America Conference on Lung Cancer 2019 meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.

After 3 decades of research, the KRAS inhibitor AMG 510 has been shown to be well tolerated by patients with non-small cell lung cancer (NSCLC) in a phase 1, first-in-human, open-label, multicenter study. Data detailing the trial’s findings were presented at the International Association for the Study of Lung Cancer (IASLC) 2019 North America Conference on Lung Cancer (NACLC 2019) in Chicago, Illinois.1

A mutation of the KRAS gene, which normally plays a role in cell signaling pathways, causes it to become oncogenic; the KRASG12C mutation is found in approximately 13% of NSCLC cases. AMG 510 is a novel small molecule therapy that “specifically and irreversibly inhibits [KRASG12C] by locking it in the inactive GDP-bound state,” the authors explained. In that state, KRAS is unable to bind to GTP and is effectively turned off.

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Bob Li, MD, of Memorial Sloan Kettering Cancer Center in New York, New York, and colleagues included 14 patients with NSCLC in the study as of April 2019. Eight of the patients were female, 93% of all patients were former smokers, and the median patient age was 65.5 years (range: 53-77). Patients were enrolled into 4 dose exploration cohorts with planned dose levels of 180 mg, 360mg, 720 mg, and 960mg, administered orally once daily. All of the patients had been previously treated with at least 2 prior lines of therapy including anti-PD1/PD-L1 therapies. According to the study abstract, 2 patients discontinued treatment because of progressive disease during the study. Six patients had a total of 10 treatment-related adverse events, grade 3 anemia and diarrhea occurred in 1 patient, respectively. Overall, decreased appetite and diarrhea were the most frequently reported AEs, occurring in 4 (29%) and 3 (21%) patients, respectively. A partial response was observed in 5 patients (1 at 180 mg, 1 at 360 mg, 3 at 960 mg), 4 patients had stable disease, and 1 patient had progressive disease.

The authors concluded that the results show “AMG 510 is well tolerated at all 4 dose levels,” adding that enrollment in the trial is continuing.


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Reference

  1. Govindan R, Fakih M, Price T, et al. Safety, efficacy, and pharmacokinetics of AMG 150, a novel  KRASG12C inhibitor, in patients with non-small cell lung cancer. Presented at: International Association for the Study of Lung Cancer (IASLC) 2019 North America Conference on Lung Cancer (NACLC 2019); October 10-12, 2019: Chicago, Illinois. Abstract OA01.06.