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sotorasib + carboplatin + pemetrexed + docetaxel + paclitaxel + pembrolizumab

Development stage
Unknown
Lead developer
Amgen
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous, Oral (sotorasib Only)
01

Overview

This is a multi-agent **combination regimen** for cancer therapy, most relevantly for advanced non-small cell lung cancer (NSCLC) with KRAS G12C mutations. The regimen contains: - **Sotorasib**: a small molecule inhibitor of KRAS G12C, which irreversibly binds to and inactivates the mutant KRAS protein, thereby inhibiting downstream oncogenic signaling. - **Carboplatin and pemetrexed:** standard platinum doublet chemotherapy agents. Carboplatin induces DNA crosslinking leading to apoptosis, while pemetrexed is an antifolate that disrupts DNA synthesis by inhibiting multiple enzymes of folate metabolism. - **Docetaxel and paclitaxel:** both are microtubule inhibitors promoting cell cycle arrest and apoptosis in dividing cells. - **Pembrolizumab:** a humanized monoclonal antibody acting as an immune checkpoint inhibitor by blocking PD-1 receptor, thereby enhancing T-cell mediated anti-tumor activity. In clinical trials, such combinations are being explored to optimize anti-tumor effects, target multiple cancer cell survival pathways, and overcome resistance, especially in KRAS G12C-mutant NSCLC. The most studied subset is sotorasib with carboplatin and pemetrexed in NSCLC, other agents such as docetaxel and paclitaxel appear as alternatives or as part of larger regimens. Pembrolizumab adds immunotherapy to the regimen, widening the attack against the tumor[1][3][5].

Brand names
pembrolizumab (Keytruda)docetaxel (Taxotere)paclitaxel (Taxol)
Other names
carboplatinpemetrexed (Alimta)
02

Targets

PDCD1 (Programmed cell death protein 1 receptor)TS (Thymidylate synthase)DHFR (Dihydrofolate reductase)DNAGART (GAR transformylase)TUBB (Tubulin (alpha and beta subunits))KRASG12C (Kirsten rat sarcoma viral oncogene homolog G12C)

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