Drug intelligence / Profile preview

STK-012 + Keytruda + chemotherapy

Development stage
Phase 2
Lead developer
Synthekine
Modality
Monoclonal Antibodies → Antibody-Based Therapeutics, Small Molecules, Recombinant Proteins and Enzymes
Administration
Intravenous, Subcutaneous
01

Overview

STK-012 + Keytruda + chemotherapy is an investigational combination immunotherapy regimen being evaluated for the treatment of advanced solid tumors, particularly first-line, PD-L1-negative nonsquamous non-small cell lung cancer (NSCLC). The regimen consists of STK-012, a first-in-class, PEGylated, alpha/beta-IL-2 receptor-biased partial agonist engineered by Synthekine; pembrolizumab (Keytruda), an anti-PD-1 monoclonal antibody developed by Merck; and standard-of-care chemotherapy (typically pemetrexed and carboplatin). STK-012 is designed to selectively stimulate CD25+ antigen-activated T cells to drive anti-tumor activity while avoiding the broad activation of natural killer (NK) cells and naïve T cells, thereby minimizing the severe toxicities (such as capillary leak syndrome) historically associated with wild-type IL-2 therapies. Pembrolizumab acts as a checkpoint inhibitor to block the PD-1/PD-L1 pathway, while chemotherapy induces immunogenic cell death and tumor debulking. This combination is currently being evaluated in the randomized Phase 2 SYNERGY-101 trial.

Other names
STK-012 + Keytruda + chemotherapySTK-012 + Keytruda + pemetrexed + carboplatinSTK-012 + PCTSTK-012 + pembrolizumab + chemotherapySTK-012 + pembrolizumab + pemetrexed + carboplatinSTK-012 plus PCTSTK012 plus PCTSTK 012 plus PCT
02

Targets

DNADHFR (Dihydrofolate reductase)GART (GAR transformylase)IL2RB (IL-2 receptor beta chain)IL2RA (Interleukin-2 receptor alpha subunit)IL2RG (Interleukin-2 receptor gamma subunit)CD274 (Programmed cell death protein 1 ligand 1)PDCD1LG2 (Programmed cell death 1 ligand 2)PDCD1 (Programmed cell death protein 1 receptor)TS (Thymidylate synthase)

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