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durvalumab + tremelimumab + cisplatin + etoposide

Development stage
Unknown
Lead developer
AstraZeneca
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules
Administration
Intravenous
01

Overview

This is a combination regimen consisting of **durvalumab** (an anti–PD-L1 monoclonal antibody), **tremelimumab** (an anti–CTLA-4 monoclonal antibody), **cisplatin** (a platinum-based chemotherapeutic), and **etoposide** (a topoisomerase II inhibitor). The combination is investigated as an initial therapy for extensive-stage small cell lung cancer (ES-SCLC), as well as metastatic non-small cell lung cancer (NSCLC), aiming to combine the immune checkpoint inhibition of durvalumab and tremelimumab with the cytotoxic effects of cisplatin and etoposide. Durvalumab blocks PD-L1 on tumor cells, preventing its interaction with PD-1, restoring anti-tumor T cell immune responses. Tremelimumab blocks CTLA-4, further enhancing T-cell activation and proliferation. Cisplatin and etoposide introduce DNA damage, resulting in cancer cell death. The CASPIAN phase 3 trial evaluated this quadruple regimen, showing numerically improved overall survival versus chemotherapy alone, but not reaching statistical significance compared to platinum-etoposide[1][4][7]. In metastatic NSCLC, a regimen including durvalumab, tremelimumab, and platinum chemotherapy has FDA approval[9]. All components are infused intravenously. Main indications studied include extensive-stage SCLC and metastatic NSCLC[1][4][7][9].

Brand names
Imfinzi (durvalumab)Imjudo (tremelimumab)
Other names
durvalumab + tremelimumab + cisplatin + etoposide
02

Targets

TOP2A (DNA topoisomerase II)CTLA-4 (Cytotoxic t-lymphocyte–associated protein 4)CD274 (Programmed cell death protein 1 ligand 1)DNA

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