TNG260

Early clinical data from an ongoing trial (NCT05887492) show increased histone acetylation and CD8+ T-cell infiltration in patient tumors treated with TNG260 and pembrolizumab. We also outline key questions for future investigation, including durability of immune response, tumor-type specificity, and biomarker strategies for patient selection and response monitoring. See related article by Ahronian et al., p. 3966.

In the tumors of patients with STK11-deficient cancers on a clinical trial (NCT05887492), treatment with a combination of TNG260 and pembrolizumab increased intratumoral histone acetylation, PD-L1 tumor proportion scores, and T cell infiltration into the tumor microenvironment. This study illustrates a promising treatment strategy for addressing immune evasion in STK11-mutant NSCLC patients.

P1/2, N=126, Recruiting, Tango Therapeutics, Inc. | Trial completion date: Jun 2025 --> Jun 2026 | Trial primary completion date: Jan 2025 --> Jan 2026

P1/2, N=126, Recruiting, Tango Therapeutics, Inc. | Not yet recruiting --> Recruiting

P1/2, N=126, Not yet recruiting, Tango Therapeutics, Inc.

Unlike previously developed pan-HDAC inhibitors, which are directly cytotoxic to cancer (and immune) cells, IND-enabling toxicology studies in rat and dog showed that TNG260 was well-tolerated at exposures predicted to be efficacious in humans, with bone marrow suppression only detectable at doses where TNG260 is no longer selective for CoREST inhibition. TNG260 clinical development will be among the first to combine the power of genetic patient selection and immunotherapy, evaluating patients with STK11 mutant cancers in a trial combining TNG260 and a checkpoint inhibitor.

It reverses the immune evasion phenotype caused by loss of STK11 and induces tumor regressions in an STK11-mutant model in combination with α-PD1. The TNG260 clinical development plan will be among the first to combine the power of genetic patient selection and immunotherapy, evaluating patients with STK11 mutant cancers in a trial combining TNG260 and a checkpoint inhibitor.