NEW YORK – Tango Therapeutics on Wednesday began treating patients with BRCA1/2-mutant or other homologous recombination-deficient cancers in a Phase I/II trial testing the activity of its USP1 inhibitor TNG348 with or without AstraZeneca's PARP inhibitor Lynparza (olaparib).
Researchers will enroll up to 140 patients in the trial. The Phase I dose-escalation portion will evaluate TNG348 alone and in combination with Lynparza in BRCA1/2-mutant or homologous recombination-deficient solid tumors. The Phase II dose-expansion portion will include arms that test the activity of TNG348 monotherapy and TNG348-Lynparza in breast, ovarian, pancreatic, and prostate cancers with the same biomarkers.
TNG348 is designed to block USP1, an enzyme that supports the survival and proliferation of homologous recombination-deficient cancer cells. In preclinical studies, TNG348 restored sensitivity to PARP inhibition in tumor models that had acquired resistance to PARP inhibitors.
Tango, based in Boston, is also studying a PRMT5 inhibitor in MTAP-deleted cancers and a CoREST complex inhibitor in STK11-mutant tumors.