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DCC-3116 + tebentafusp is an investigational combination therapy being evaluated for the treatment of HLA-A*02:01-positive metastatic uveal melanoma. The combination consists of **DCC-3116** (also known by the development code **DCSZ11**), a potent and selective small-molecule inhibitor of the Unc-51 like autophagy activating kinases 1 and 2 (**ULK1/2**), and **tebentafusp** (**Kimmtrak**), a first-in-class bispecific T-cell receptor (TCR) T-cell engager. DCC-3116 is designed to inhibit autophagy, a cellular stress-response mechanism that tumors utilize to survive metabolic stress and resist immune-mediated killing. Tebentafusp targets the melanocyte-associated antigen **gp100** presented by HLA-A*02:01 and redirects T cells to the tumor via a CD3-binding domain. The rationale for this combination is that inhibiting autophagy may sensitize tumor cells to T-cell mediated cytotoxicity and overcome potential resistance mechanisms to T-cell engager therapy.
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