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    Association details:
    Biomarker:KRAS G12C
    Cancer:Colorectal Cancer
    Drug:Lumakras (sotorasib) (KRAS G12C inhibitor)
    Direction:Sensitive
    Evidence:
    Evidence Level:
    Sensitive: C1 - Off-label
      (Approved for Non Small Cell Lung Cancer)
    New
    Title:

    LUMAKRAS® (SOTORASIB) RECEIVES APPROVAL IN JAPAN FOR PATIENTS WITH KRAS G12C-MUTATED ADVANCED NON-SMALL CELL LUNG CANCER

    Excerpt:
    Amgen...announced that LUMAKRAS® (sotorasib) has been approved in Japan for the treatment of KRAS G12C-mutated positive, unresectable, advanced and/or recurrent non-small cell lung cancer (NSCLC) that has progressed after systemic anticancer therapy.
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Source:
    clinicaltrialsregister.eu
    Title:

    Clinical study to investigate the safety, tolerability, pharmacokinetics, pharmacodynamics and efficacy of AMG 510

    Excerpt:
    ...For all parts except 2e: Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing. ...
    Trial ID:
    2018-001400-11
    Evidence Level:
    Sensitive: C2 – Inclusion Criteria
    New
    Source:
    clinicaltrials.gov
    Title:

    Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101)

    Excerpt:
    ...- Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing performed according to in-country requirements....
    Trial ID:
    CodeBreak101
    Less C2 evidence
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Lancet Oncol
    Title:

    Sotorasib for previously treated colorectal cancers with KRASG12C mutation (CodeBreaK100): a prespecified analysis of a single-arm, phase 2 trial

    Published date:
    12/14/2021
    Excerpt:
    This analysis is a prespecified analysis triggered by the phase 2 colorectal cancer cohort...62 patients with KRASG12C-mutant colorectal cancer had been enrolled...received at least one dose of sotorasib monotherapy. Objective response was observed in six (9·7%, 95% CI 3·6–19·9) of 62 patients, all with partial response.
    DOI:
    https://doi.org/10.1016/S1470-2045(21)00605-7
    Trial ID:
    CodeBreak 100
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    N Engl J Med
    Title:

    KRAS G12C Inhibition with Sotorasib in Advanced Solid Tumors

    Published date:
    09/20/2020
    Excerpt:
    We conducted a phase 1 trial of sotorasib in patients with advanced solid tumors harboring the KRAS p.G12C mutation….In the subgroup with colorectal cancer, 7.1% (3 patients) had a confirmed response, and 73.8% (31 patients) had disease control; the median progression-free survival was 4.0 months (range, 0.0+ to 11.1+)....Sotorasib showed encouraging anticancer activity in patients with heavily pretreated advanced solid tumors harboring the KRAS p.G12C mutation.
    DOI:
    10.1056/NEJMoa1917239
    Trial ID:
    CodeBreak 100
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    ASCO 2020
    Title:

    CodeBreak 100: Activity of AMG 510, a novel small molecule inhibitor of KRASG12C, in patients with advanced colorectal cancer.

    Published date:
    05/13/2020
    Excerpt:
    In pts with heavily pretreated KRAS p.G12C mutant CRC, AMG 510 monotherapy was well tolerated, with the majority of pts achieving disease control.
    DOI:
    10.1200/JCO.2020.38.15_suppl.4018
    Trial ID:
    CodeBreak 100
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    ASCO 2020
    Title:

    CodeBreak 100: Phase I study of AMG 510, a novel KRASG12C inhibitor, in patients (pts) with advanced solid tumors other than non-small cell lung cancer (NSCLC) and colorectal cancer (CRC).

    Published date:
    05/13/2020
    Excerpt:
    AMG 510 was well tolerated and demonstrated clinical activity in pts with advanced KRAS p.G12C mutant solid tumors other than NSCLC and CRC.
    DOI:
    10.1200/JCO.2020.38.15_suppl.3511
    Trial ID:
    CodeBreak 100
    Evidence Level:
    Sensitive: C3 – Early Trials
    Source:
    Clin Colorectal Cancer
    Title:

    KRAS G12C Metastatic Colorectal Cancer: Specific Features of a New Emerging Target Population

    Published date:
    05/12/2020
    Excerpt:
    A total of 839 KRAS-mutated mCRC cases were included in the main patient population. A total of 145 patients (17%) had KRAS G12C mutation...KRAS G12C mutation was associated with shorter overall survival compared to other KRAS mutations (hazard ratio, 1.32; 95% confidence interval, 1.07-1.63; P = .009). Such results were confirmed in the external validation cohort.
    DOI:
    10.1016/j.clcc.2020.04.009
    Evidence Level:
    Sensitive: D – Preclinical
    Source:
    Cancer Discov
    Title:

    EGFR blockade reverts resistance to KRAS G12C inhibition in colorectal cancer

    Published date:
    05/19/2020
    Excerpt:
    Contradicted Evidence: To investigate the cause of the limited efficacy of KRAS G12C inhibitors in CRC, we examined the effects of AMG510 in KRAS G12C CRC cell lines….Although upstream activation of several RTKs interferes with KRAS G12C blockade, we identify EGFR signaling as the dominant mechanism of CRC resistance to KRAS G12C inhibitors.
    DOI:
    10.1158/2159-8290.CD-20-0187