Zenith Epigenetics Ltd. announced the initiation of a Phase 2b Triple Negative Breast Cancer clinical trial combining ZEN-3694 + Pfizer Inc.'s Talzenna (talazoparib). The trial will continue to evaluate the efficacy and safety of this combination in patients with locally advanced or metastatic germline wild type BRCA1/2 TNBC. This Phase 2b trial is an extension of the recently completed Phase 1b/2 trial which met its primary efficacy endpoint of clinical benefit rate comprised of objective responses plus stable disease and which showed that the combination regimen was well tolerated.

The Phase 2b extension will enroll patients who have previously been treated with a TROP2 antibody drug conjugate for locally advanced or metastatic disease. In the United States, talazoparib is currently approved under the brand name TALZENNA, which is a poly polymerase inhibitor indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer. Single agent PARPi are approved for gBRCAm HER2-negative locally advanced or metastatic breast cancer, as both PARP inhibition and non-functioning DNA repair proteins BRCA1/2 are required to block DNA repair and kill tumor cells (synthetic lethality).

Preclinical and clinical data has shown that BET inhibition may reduce the levels of DNA repair proteins such as BRCA1/2 and RAD51 and thus create synthetic lethality in wildtype BRCA1/2 TNBC tumors when combined with PARP inhibition.