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JAB-3312 + pembrolizumab is a **combination therapy comprising JAB-3312, a selective allosteric inhibitor of SHP2 (also known as sitneprotafib), and pembrolizumab, a monoclonal antibody targeting programmed cell death protein 1 (PD-1)**. JAB-3312 targets SHP2 (PTPN11), inhibiting oncogenic RTK/RAS/MAPK signaling, which plays a crucial role in many tumor types, and also blocks immunosuppressive signaling downstream of PD-1, thereby enhancing anti-tumor immunity by activating T cells. Pembrolizumab is a well-established immune checkpoint inhibitor that blocks PD-1, augmenting the immune system's ability to target and destroy tumor cells. The combination is under investigation for the treatment of various advanced solid tumors, with JAB-3312 potentiating both direct anti-tumor effects and immunotherapy efficacy by reversing immune evasion mechanisms. Both drugs are administered by different routes—JAB-3312 orally and pembrolizumab intravenously—and the pairing has shown promise in preclinical studies and is currently in early-phase clinical trials for a range of solid tumors, including non-small cell lung cancer and esophageal squamous cell carcinoma.
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