Study of TNG260 and an Anti-PD Antibody in STK11 Mutated Solid Tumors

A Phase 1/2, Open-Label Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Efficacy of TNG260 as Single Agent and in Combination With an Anti-PD-1 Antibody In Patients With STK11 Mutated Advanced Solid Tumors. This sheet concerns all solid tumors.

TNG260 is a selective, orally effective inhibitor of HDAC1 and CoREST complex. TNG260 reshapes the tumor immune microenvironment, reduces immunosuppressive neutrophil infiltration, promotes effector T cell recruitment, and reverses anti-PD-1 resistance caused by STK11 deficiency by inhibiting the activity of the CoREST-HDAC1 complex.

Pembrolizumab is a humanized monoclonal antibody (IgG4) directed against the PD-1 receptor, located on the surface of T lymphocytes. It blocks the inhibition of T lymphocytes by preventing the binding of PD-1 ligands (PD-L1 and PD-L2 located on the surface of tumor cells) to the PD-1 receptor. This has the effect of inducing anti-tumor immunity by activating tumor-specific cytotoxic T lymphocytes in the tumor microenvironment.

This non randomised study has a sequential assignment:

Experimental - Dose Escalation: Participants with STK11-mutant solid tumors will receive escalating doses of TNG260 in combination with pembrolizumab to estimate the MTD.

Experimental - Dose Expansion in Advanced or Metastatic Solid Tumors: Participants with STK11-mutant solid tumors (including but not limited to pancreatic, endometrial, cervical, breast, and carcinoma of unknown primary) will receive TNG260 at the identified RP2D in combination with pembrolizumab

Inclusion Criteria:

• All participants must have documented STK11 mutation in a solid tumor, which is identified through a validated analytical method
• Has confirmed histologic or cytologic diagnosis of a locally advanced or metastatic solid tumor.

Exclusion Criteria:

• Known allergies, hypersensitivity, or intolerance to TNG260, PD-1 antibody or its excipients
• Impairment of GI function or disease that may significantly alter the absorption of oral TNG260
• Central nervous system metastases associated with progressive neurological symptoms.