Amgen vs. Mirati KRAS inhibitors siege colorectal cancer

Author: Plus One

This year is a year of milestone progress for KRAS inhibitors
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In colorectal cancer (CRC), the incidence of KRASG12C mutations is between 3% and 4%, second only to NSCLC
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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
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CRC clinical data of Adagrasib and Sotorasib (Lumakras)

From: EvaluatePharma

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
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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
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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)
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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)
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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
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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)
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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
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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
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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%
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Adagrasib (MRTX849)'s Chinese rights belong to Zai Lab
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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
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And Amgen's Sotorasib (AMG-510) is developed in cooperation with BeiGene in China
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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
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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)
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In terms of safety, the incidence of grade 3/4 TRAEs was 13%
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Amgen’s CodeBreaK project has enrolled more than 800 patients involving 13 cancer types
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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
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A phase 2 randomized study, CodeBreaK201, will evaluate Sotorasib as a first-line treatment in patients with stage IV KRASG12C mutant NSCLC
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