Tango Therapeutics, Inc. a clinical-stage biotechnology company committed to discovering and delivering the next generation of precision cancer medicines, today announced that the first patient has been dosed in the phase 1/2 trial evaluating TNG260 in combination with pembrolizumab in patients with STK11-mutant cancers. TNG260 is a first-in-class inhibitor of the CoREST complex .
“The TNG260 phase 1/2 clinical trial is the first trial to use genetic patient selection in combination with checkpoint inhibitor therapy to reverse the cancer-specific immune evasion caused by STK11 loss of function mutations. Resistance to immunotherapy is a major challenge faced by patients with STK11-mutant cancers, which TNG260 is specifically designed to overcome,” said Adam Crystal, M.D., Ph.D., President of Research and Development of Tango Therapeutics. “Our pipeline of precision oncology treatments based on synthetic lethality has advanced significantly this year, as we now have initiated three clinical trials.”
The phase 1/2 trial will evaluate the safety, pharmacokinetics (PK), pharmacodynamics and efficacy of TNG260, with a one cycle single agent run-in phase to evaluate the safety and PK of TNG260, in combination with pembrolizumab, in patients with locally advanced or metastatic solid tumors with an STK11 loss-of-function mutation. STK11 loss-of-function mutations occur in approximately 15% of non-small cell lung cancer, 15% of cervical, 10% of carcinoma of unknown primary, 5% of breast and 3% of pancreatic cancers. Based on preclinical xenograft studies and retrospective clinical analyses, the majority of STK11-mutant cancers are thought to have primary resistance to checkpoint inhibition.
The CoREST complex plays a central role in regulating immunomodulatory signaling in STK11-mutant cancers. In preclinical studies, TNG260 reverses the immune evasion effect of STK11 loss-of-function mutations, restoring sensitivity to an anti-PD-1 antibody, inducing complete remissions in the majority of animals and creating immune memory that prevents re-implantation and regrowth of the tumor.
In April 2023, the U.S. Food and Drug Administration granted Fast Track designation for TNG260 in combination with an anti-PD-1 antibody for the treatment of patients with previously treated advanced non-small cell lung cancer with STK11-mutations.
About Tango Therapeutics
Tango Therapeutics is a clinical-stage biotechnology company dedicated to discovering novel drug targets and delivering the next generation of precision medicine for the treatment of cancer. Using an approach that starts and ends with patients, Tango leverages the genetic principle of synthetic lethality to discover and develop therapies that take aim at critical targets in cancer. This includes expanding the universe of precision oncology targets into novel areas such as tumor suppressor gene loss and their contribution to the ability of cancer cells to evade immune cell killing.