Combination: obrixtamig + cisplatin + etoposide

The combination of obrixtamig, cisplatin, and etoposide is a therapeutic regimen primarily investigated for the treatment of advanced malignancies, such as small cell lung cancer (SCLC) and other high-grade neuroendocrine tumors. Obrixtamig (IBI363) is a first-in-class bispecific antibody-cytokine fusion protein designed to target PD-1 and the IL-2 receptor, thereby reactivating exhausted T-cells and promoting their proliferation within the tumor microenvironment [Innovent Biologics, 2023]. Cisplatin is a platinum-based chemotherapy that induces cell death through DNA cross-linking, while etoposide is a topoisomerase II inhibitor that causes catastrophic DNA strand breaks [StatPearls, 2023; StatPearls, 2024]. By combining these cytotoxic agents with a next-generation immunotherapy, the regimen aims to leverage the release of tumor antigens from dying cells to prime a more robust and durable immune response. This triplet therapy is currently being evaluated in clinical trials to determine if it can improve progression-free and overall survival compared to standard-of-care chemotherapy alone [ClinicalTrials.gov, 2024].

Other names

IBI363 plus Cisplatin and EtoposideObrixtamig + EP regimenPD-1/IL-2 bispecific plus platinum-etoposide chemotherapy

This combination therapy utilizes a multi-pronged approach: obrixtamig (IBI363) is a bispecific fusion protein that blocks the Programmed cell death protein 1 (PD-1) pathway while simultaneously delivering an Interleukin-2 (IL-2) signal to activate and expand tumor-infiltrating T-cells [Innovent Biologics, 2023]. Cisplatin acts as a cytotoxic agent by forming inter-strand and intra-strand DNA cross-links, which inhibit DNA replication and transcription [StatPearls, 2023]. Etoposide further induces DNA damage by inhibiting DNA topoisomerase II, preventing the re-ligation of DNA strands and leading to double-strand breaks [StatPearls, 2024]. Together, these agents promote immunogenic cell death and enhance the anti-tumor immune response.