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**LNS8801 + pembrolizumab** is an investigational combination therapy being evaluated in clinical trials for treatment-refractory advanced solid tumors, including melanoma (cutaneous and uveal), non-small cell lung cancer, and a range of other cancers. LNS8801 is an oral, selective, small molecule agonist of the G-protein coupled estrogen receptor (GPER). Pembrolizumab is a monoclonal antibody immune checkpoint inhibitor targeting programmed cell death protein 1 (PD-1). LNS8801 acts by promoting melanocytic differentiation, reducing c-Myc protein, inhibiting tumor cell proliferation and invasion, and enhancing immune recognition, with GPER as its primary target. When combined with pembrolizumab (an anti-PD-1 therapy that potentiates immune-mediated antitumor effects), the combination has demonstrated tolerability and preliminary evidence of clinical benefit, especially for patients who have progressed on, or are refractory to, prior immune checkpoint inhibitors. The combination is being evaluated in multiple Phase 1 and Phase 2 clinical trials, notably in patients with metastatic uveal melanoma, cutaneous melanoma, non-small cell lung cancer expressing PD-L1, and various other solid tumors[1][2][3][4][5].
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