Finally waiting for you, the first KRAS gene targeting drug AMG510 has been approved for marketing

KRAS gene mutations in lung cancer are called "the most difficult mutations".
There have been no targeted drugs available, and the effect of chemotherapy is also poor.

KRAS mutations account for about 25% of non-small cell lung cancer mutations, of which G12C site mutations account for 13% of non-small cell lung cancer.

For many years, the development of targeted drugs for KRAS gene mutations has been urgent.

Finally, we waited for the first light.

On May 28, 2021, the US FDA approved Lumakras (Sotorasib), the first targeted drug for KRAS gene mutations, code-named AMG510 and Chinese name Sotorasib.

Figure 1.
Sotorasib (AMG510) approved by the US FDA for marketing AMG510 approved indications: KRAS gene G12C-positive non-small cell lung cancer that has undergone at least one systemic treatment and has progressed.

CodeBreak 100 clinical trial confirms the efficacy of AMG510 In a Phase II clinical trial of CodeBreak 100, 124 patients with locally advanced or metastatic non-small cell lung cancer with G12C mutations in the KRAS gene were included.

These patients progressed after at least one systemic treatment, so they were enrolled and started using AMG510 at a dose of 960 mg.

Figure 2.
The efficacy data of AMG510 in the treatment of non-small cell lung cancer.
The published efficacy data are as follows: 36% of patients have significantly reduced tumor lesions and achieved partial clinical remission; 58% of patients have a treatment response time of more than 6 months.

The median progression-free survival of patients who achieved clinical partial remission was 10.
9 months.

The median progression-free survival of patients with stable disease has reached 4 months.

Based on the above better efficacy data, the US FDA has accelerated the approval of AMG510 for marketing, and also approved a kit for the detection of the G12C site of the KRAS gene.

If the patient fails to detect the KRAS mutation in the blood sample, it is recommended to use a punctured tissue sample for testing.

ASCO subgroup analysis in 2021, patients in each group can benefit.
At the ASCO conference in 2021, the results of a study on AMG510 were announced.

The study analyzed the efficacy of the drug and the patient's gene mutations to determine whether the frequency of gene mutations will affect the efficacy of the drug.

During the treatment of patients with AMG510, the second-generation gene sequencing technology will be used to analyze the mutations at the G12C site of the KRAS gene, including gene mutation frequency MAF (sometimes called abundance), tumor mutation burden TMB, etc.

Figure 3.
The treatment response rate of AMG510 in the treatment of the KRAS mutant lung cancer subgroup is shown in the above figure.
Any subgroup can obtain a good treatment response rate during the treatment with AMG510.

The common mutation of TP53 gene and STK11 gene does not affect the patient's benefit from AMG510 treatment.

Tumor mutational burden TMB is also not related to the response rate of treatment, and the mutation frequency (MAF) of the G12C site of the KRAS gene is also not related to the response rate of treatment.

The US FDA approved the drug with a dose of 960 mg, and requires the drug to undergo clinical trials after it is marketed to verify whether the lower dose of AMG510 also has the corresponding therapeutic effect.

What are the precautions for medication? The main adverse reactions caused by AMG510 are diarrhea, musculoskeletal pain, nausea, fatigue, liver damage and cough.

The US FDA has also given corresponding medication guidance recommendations: Guidance recommendations 1.
If the patient has symptoms of interstitial pneumonia, the drug needs to be stopped immediately, and if it is diagnosed as interstitial pneumonia, the drug should be permanently stopped.

2.
Liver function tests need to be performed before using the drug.
If liver damage occurs, you need to stop using the drug.

3.
Acid reducers and related drugs that affect liver drug metabolism should not be used during the use of this drug, that is, try not to take traditional Chinese medicine.

It is expected that the strong combination of AMG510 and a variety of drugs KRAS gene mutations exist in a variety of tumors, and the probability of mutation is relatively high.

The AMG510 targeted drug was approved for marketing, breaking the curse of non-targeted KRAS mutations for many years, and bringing more possibilities for fighting tumors.

In future treatments, AMG510 is likely to be combined with multiple drugs.

Such as interspersed therapy with chemotherapy or immunotherapy, or adjuvant therapy and neoadjuvant therapy for lung cancer.

The patient's survival benefit will be greatly improved.

From scratch, the process is difficult.

But we believe that more suitable drugs will appear in the future.

Cancer degree accompanies everyone through the catastrophe and welcomes tomorrow.

At present, clinical trials of targeted drugs for KRAS gene mutations are officially launched in China.
You can search and download the Cancer Degree APP and click on the homepage "New Drug Recruitment" to register.

You can also click on the "Global Clinical Trials" applet below to sign up for clinical trials of KRAS gene mutations.

References https://meetinglibrary.
asco.
org/record/196931/abstracthttps://meetinglibrary.
asco.
org/record/200635/abstract Click below to learn more about clinical trial projects in the past review slide to view more past content