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LY4050784 + pembrolizumab + pemetrexed + cisplatin
- Development stage
- Unknown
- Lead developer
- Eli Lilly
- Modality
- Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
- Administration
- Oral (LY4050784), Intravenous (pembrolizumab), Intravenous (pemetrexed), Intravenous (cisplatin)
01
Overview
This combination regimen consists of four agents: **LY4050784** (a selective oral small-molecule inhibitor of SMARCA2/BRM), **pembrolizumab** (a monoclonal antibody programmed death-1 [PD-1] immune checkpoint inhibitor), **pemetrexed** (an antifolate chemotherapy), and **cisplatin** (a platinum-based chemotherapy). LY4050784 is being investigated in SMARCA4/BRG1-altered advanced solid tumors for its synthetic lethality in SMARCA4-deficient cancers by inhibiting SMARCA2 activity. Pembrolizumab blocks PD-1, reactivating T-cell antitumor responses. Pemetrexed inhibits folate-dependent enzymes involved in DNA synthesis, and cisplatin causes DNA crosslinking, leading to apoptosis. This combination is under investigation primarily for treatment of advanced/metastatic solid tumors, particularly non-small cell lung cancer with specific molecular alterations[1][2][3][4].
- Other names
- cisplatinpembrolizumabpemetrexedLY4050784LY-4050784LY 4050784LY4050784 + pembrolizumab + pemetrexed + cisplatin
02
Targets
PDCD1 (Programmed cell death protein 1 receptor)DNASMARCA2 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin subfamily A member 2)DHFR (Dihydrofolate reductase)
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