====== Adagrasib ======

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**Adagrasib** (brand name **Krazati**) is an oral, small-molecule inhibitor that **specifically targets [[KRAS G12C mutation]]s**, which are commonly found in certain cancers, including:

* **[[Non-small cell lung cancer]] (NSCLC)**

* **Colorectal cancer**

* **Pancreatic cancer**

===== Key Points =====

* **Mechanism of action**:
  Adagrasib irreversibly binds to the **KRAS G12C mutant protein**, locking it in its inactive state. This prevents the downstream signaling that promotes tumor growth.

* **Approved indication**:
  As of late 2022, the FDA approved adagrasib for **NSCLC with KRAS G12C mutations** in patients who have received at least one prior systemic therapy.

* **Combination therapy potential**:
  Adagrasib is being studied in **combination with other agents**, such as:

  * **Immune checkpoint inhibitors** (e.g., pembrolizumab)
  * **EGFR inhibitors** in colorectal cancer (e.g., cetuximab)
  * **SHR inhibitors or MEK inhibitors** in preclinical models

Advantages over sotorasib (another KRAS G12C inhibitor):

Some studies suggest adagrasib may have better **central nervous system penetration**, offering hope for patients with brain metastases. 

[[Adagrasib for Non-small cell lung cancer intracranial metastases]]