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    Home > Biochemistry News > Biotechnology News > Amgen vs. Mirati KRAS inhibitors siege colorectal cancer

    Amgen vs. Mirati KRAS inhibitors siege colorectal cancer

    • Last Update: 2021-10-11
    • Source: Internet
    • Author: User
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    Author: Plus One

    This year is a year of milestone progress for KRAS inhibitors
    .


    In May, Amgen Sotorasib was approved for use in KRASG12C mutant non-small cell lung cancer (NSCLC), symbolizing the first breakthrough in the "Holy Grail of Tumor Targeting Drugs"


    In colorectal cancer (CRC), the incidence of KRASG12C mutations is between 3% and 4%, second only to NSCLC
    .


    Therefore, CRC is also regarded as an important potential indication for KRASG12C inhibitors


    Fortunately, at the 2021 ESMO conference that is being held from September 16 to 21, the use of KRASG12C inhibitors in the treatment of CRC has finally reappeared
    .


    Amgen announced the Phase 1b/2 clinical data of Sotorasib combination therapy for colorectal cancer, and gratifying data was obtained through the exploration of combination therapy; and Mirati reported as LBA Adarasib monotherapy and combination therapy for the treatment of CRC Phase 1/2 According to clinical data, the two new drugs have shown encouraging effects


    CRC clinical data of Adagrasib and Sotorasib (Lumakras)

    From: EvaluatePharma

    Adagrasib: single drug ORR up to 22%

    Adagrasib: single drug ORR up to 22%

    Adagrasib is a KRASG12C inhibitor developed by Mirati.
    It started clinical development almost at the same time as Amgen's Sotorasib and belongs to the first echelon of global development of KRASG12C inhibitors
    .

    KRYSTAL-1 (NCT03785249) is a multi-cohort phase 1/2 study to evaluate the efficacy of Adagrasib (MRTX849) as a single agent or in combination with cetuximab in patients with advanced solid tumors with KRASG12C mutations
    .

    The clinical data (LBA6) published at the ESMO conference this time are CRC cohort data, including adagrasib600mgBID monotherapy (Phase 1/2) and adagrasib600mgBID+cetux400mg/m2 followed by 250mg/m2QW or 500mg/m2Q2W (Phase 1b)
    .


    The study endpoints include safety, PK, and clinical activity


    For the monotherapy group, as of May 25, 2021, a total of 46 CRC patients (50% women; median age 58 years; 3 median previous treatment lines) received adagrasib monotherapy (median follow-up: 8.
    9 Month)
    .


    The results showed that among the 45 evaluable patients, ORR was 22% (10/45, including 1 unconfirmed PR still under study), DCR was 87% (39/45), and median DOR was 4.


    In terms of safety, 91% of patients had any grade of TRAE, 30% of patients had grade 3/4 events, and no grade 5 events occurred
    .

    As for the combination therapy group, as of July 9, 2021, 32 CRC patients (53% women; median age 60 years; median frontline treatment 3 times) received adagrasib+cetux treatment (median follow-up 7 months)
    .


    The results showed that in 28 evaluable patients, ORR was 43% (12/28, including 2 unconfirmed PRs still under study), and DCR was 100%


    In terms of safety, 100% of patients had any grade of TRAEs, 16% of patients had grade 3/4 events, and no grade 5 events occurred
    .

    The data reported in this report shows that Adagrasib is well tolerated as a single-agent therapy.
    Both single-agent and combined cetuximab show promising clinical activity in patients with KRASG12C mutant CRC who have failed multi-line therapy
    .


    Currently, Mirati is carrying out Phase 3 clinical trials to evaluate the efficacy and safety of combination therapy in the second-line treatment of KRASG12C mutant CRC patients (NCT04793958)


    Adagrasib is Mirati’s key product.
    Earlier, because Amgen’s Sotorasib was the first to obtain accelerated FDA approval, Mirati’s stock price suffered a heavy blow and plunged 35%
    .


    However, from the current data, Mirati may be expected to overtake the car in colorectal cancer indications


    Adagrasib (MRTX849)'s Chinese rights belong to Zai Lab
    .
    On June 1, 2021, Zai Lab obtained the Greater China rights of this product with an advance payment of US$65 million and a milestone amount of US$273 million
    .
    And Amgen's Sotorasib (AMG-510) is developed in cooperation with BeiGene in China
    .

    Amgen Sotorasib: The potential of combination therapy is emerging

    Amgen Sotorasib: The potential of combination therapy is emerging

    At the meeting on the 17th, Amgen has announced the KRASG12C inhibitor Sotorasib combined with its self-developed EGFR monoclonal antibody panitumumab (panitumumab) for the treatment of patients with KRASG12C mutation advanced/metastatic colorectal cancer Phase 1b/2 clinical CodeBreak101 study (NCT04185883) ) Part of the data
    .

    The results showed that this combination achieved 27% ORR and 81% DCR in 26 evaluable patients (including 5 patients who progressed after receiving Sotorasib in the past)
    .
    In terms of safety, the incidence of grade 3/4 TRAEs was 13%
    .

    Amgen’s CodeBreaK project has enrolled more than 800 patients involving 13 cancer types
    .
    The global multicenter Phase 3 clinical CodeBreaK200 has been enrolled, and Amgen’s Phase 1b study CodeBreaK101 is still studying Sotorasib monotherapy and combination therapy for a variety of different advanced solid tumors, and is still being enrolled
    .
    A phase 2 randomized study, CodeBreaK201, will evaluate Sotorasib as a first-line treatment in patients with stage IV KRASG12C mutant NSCLC
    .

    Note: The original text has been deleted

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