What is the current progress of clinical trials of Adagrasib?

Adagrasib is a tyrosine kinase inhibitor targeting the KRAS G12C mutation, developed by Mirati Therapeutics. As an important KRAS G12C inhibitor after sotorasib, adagrasiib has attracted much attention due to its longer half-life, stronger tissue penetration and potential central nervous system activity. At present, adagrasib has entered clinical research and limited marketing stages in many countries, and is mainly used to treat non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and other solid tumors with KRAS G12C mutations.

In the field of NSCLC, the KRYSTAL-1 trial of adagrasib provided key supporting data. Studies have shown that in patients with KRAS G12C mutated NSCLC who have previously received standard treatment, the objective response rate (ORR) of adagrasiib is about 43%, the median progression-free survival (PFS) is 6.5 months, and the median overall survival (OS) is 12.6 months, showing a comparable or even slightly better efficacy than sotorasib. More importantly, the drug has also shown clinical activity in some patients with brain metastases, suggesting that it is expected to make up for the lack of central penetration of sotoraxib.

In terms of colorectal cancer, adagrasib is conducting multiple combination treatment trials such as KRYSTAL-10, especially in combination with EGFR monoclonal antibodies such as cetuximab (Cetuximab). In preliminary data, the ORR of the combination treatment group reached 46%, which is much higher than the historical data of monotherapy, showing the synergistic potential of KRAS G12C inhibitor + EGFR inhibition, which also opens a new breakthrough for future CRC treatment. Mirati is also exploring possible applications in other solid tumors such as pancreatic cancer.
As of early 2025, adagrasib has received accelerated approval from the US FDA for the treatment of NSCLC patients with KRAS G12C mutations, and continues to promote more clinical trial registration and indication expansion in many countries around the world. At the same time, its clinical trials in combination with immunotherapy, anti-angiogenic drugs and other targeted drugs are also progressing steadily. As data gradually accumulates, adagrasibu is expected to become one of the core drugs for KRAS G12C targeted therapy alongside sotorasibu, especially in brain metastasis and combination therapy, showing unique advantages.
Reference: https://www.krazati.com/