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CLN-617 + pembrolizumab is a combination therapy under clinical investigation for advanced solid tumors, consisting of CLN-617—a first-in-class, intratumorally injected fusion protein that delivers both interleukin-2 (IL-2) and interleukin-12 (IL-12) within a single molecule (fused with LAIR2 and human serum albumin domains for enhanced tumor retention)—and pembrolizumab, a PD-1-blocking monoclonal antibody. CLN-617 is designed to locally stimulate a strong antitumor immune response by synergistically activating and proliferating T cells and NK cells, while pembrolizumab blocks PD-1 mediated immune checkpoints, enabling sustained tumor rejection and overcoming immune evasion. Preclinical studies suggest CLN-617 can “heat up” immune-cold tumors and, in combination with pembrolizumab, drive systemic immune activity leading to regression of both injected and distant tumors. The combination is currently being investigated in a phase 1, open-label trial for advanced solid tumors, including metastatic melanoma and squamous cell carcinoma of the head and neck[1][2][3][5][7][8].
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