- AMG 510 molecule specifically and irreversibly inhibits KRASG12C.
- At the tested dose levels, it has a favourable safety profile and a promising anti-tumour activity as monotherapy in Non-Small Cell Lung Cancer (NSCLC) with the mutation.
- These data underscore the potential to close the gap in the treatment of NSCLC patients with previously treated KRASG12C-mutated disease.
Why this matters
- KRASG12C mutation is present in approximately 13% of lung cancer.
- Currently, no approved therapies are targeting this mutation.
- A phase 1, first-in-human, open-label, multicentre study is ongoing to evaluate the safety, tolerability, pharmacokinetics and efficacy of AMG 510 in adults with locally-advanced or metastatic solid malignancies harbouring KRASG12C mutation.
- 34 NSCLC patients were included by the cut-off date, 23 being evaluable for efficacy.
- Four doses were tested: 180 mg, 360 mg, 720 mg, 960 mg.
- Safety and dose-limiting toxicities are the primary endpoints.
- Key secondary endpoints include objective response rate (ORR), duration of response (DOR), progression-free survival (PFS) and pharmacokinetic (PK).
- The 960 mg oral daily dose was identified as the expansion dose and recommended phase 2 dose.
- No dose-limiting toxicities were reported and no treatment-related adverse events (TRAEs) occurred leading to treatment discontinuation.
- 35.5% of patients reported TRAEs, mostly of grade 1 or 2; no grade 4 or higher TRAEs were reported.
- Among the 13 evaluable patients treated with 960 mg, 54% and 46% achieved a partial response and a stable disease, respectively, for a disease control rate of 100%.
- Amgen Inc.
“These data definitely establish KRASG12C as a clinical druggable target in human cancer. There are some key questions to be addressed, including the role of molecular diversity of KRAS in determining AMG 510 efficacy”. Jon Zugazagoitia. Department of Medical Oncology, Hospital 12 de Octubre. Madrid, Spain.