Synthekine’s STK-012 Shows Promising Efficacy in PD-L1-Negative NSCLC

Synthekine has announced encouraging early data from a Phase Ia/Ib study evaluating STK-012 in first-line PD-L1–negative nonsquamous non-small cell lung cancer (NSCLC). The IL-2 receptor α/β-biased partial agonist was tested in combination with pembrolizumab and chemotherapy in 21 efficacy-evaluable participants. Of these, 17 had PD-L1 expression below 1%, and 15 carried tumour suppressor gene mutations such as SMARCA4, STK11, or KEAP1, or had mucinous histology—features associated with immune resistance.

STK-012 selectively activates antigen-activated T cells, enhancing antitumour response while minimizing IL-2–related toxicity. The therapy demonstrated a high response rate and a favourable safety profile in this difficult-to-treat population.

The results suggest STK-012 may convert immune-resistant “desert” tumours into responders. The findings, presented at the 2025 Society for Immunotherapy of Cancer Annual Meeting, support advancing STK-012 into a randomized Phase II trial.

12-11-2025