Sotorasib is an oral inhibitor targeting KRASG12C mutations, primarily used to treat non-small cell lung cancer and colorectal cancer with specific gene mutations. Its indications include monotherapy for non-small cell lung cancer and combination therapy with pembrolizumab for colorectal cancer, which requires confirmation of mutation status through genetic testing before use.

Non small cell lung cancer (NSCLC)

Suitable for adult patients with locally advanced or metastatic non-small cell lung cancer with KRASG12C mutation, who must have received at least one systemic treatment in the past. As a second-line monotherapy, it can significantly delay disease progression.

2. Metastatic colorectal cancer (mCRC)

Combination therapy with panitumumab for metastatic colorectal cancer with KRASG12C mutation is suitable for patients who have previously failed chemotherapy with fluoropyrimidine, oxaliplatin, or irinotecan. The joint plan was approved by the FDA in January 2025.

3 target specificity

Only effective for tumors with G12C mutation at codon 12 of KRAS gene, by covalently binding to the switch pocket of the mutant protein, blocking the activation of abnormal signaling pathways. The mutation status must be confirmed through molecular testing before medication.

4. Basis of therapeutic effect

Sotolabib specifically inhibits GTPase activity and blocks abnormal signaling pathways by covalently binding to KRASG12C mutant protein. The FDA is accelerating its approval for the treatment of KRASG12C mutant non-small cell lung cancer and expanding it to colorectal cancer combination therapy by 2025.

5 Indicative effects

(1) Non small cell lung cancer: As a monotherapy, it has a clear therapeutic effect on locally advanced or metastatic patients who have previously received systemic treatment.

(2) Colorectal cancer: Combination with panitumumab can significantly delay disease progression in KRASG12C mutant metastatic patients.

6 Precautions for use

Strict adherence to indications is required and is only effective for patients with KRASG12C mutation. During treatment, liver function and adverse reactions should be monitored, and medication for special populations should be carefully evaluated.