Tango Therapeutics, Inc. announced that the first patient has been dosed in the phase 1/2 trial evaluating TNG348 as a single agent and in combination with olaparib, a PARP inhibitor, in patients with BRCA1/2-mutant or other HRD+ (homologous recombination deficient) cancers. TNG348 is a novel, selective inhibitor of USP1 (ubiquitin-specific protease 1). The phase 1/2 trial will evaluate the safety, pharmacokinetics, pharmacodynamics and efficacy of TNG348 as a single agent and in combination with olaparib, a PARP inhibitor, in patients with BRCA1/2-mutant and other HRD+ cancers.

HRD+ cancers, including BRCA1/2 mutations, represent up to 50% of ovarian cancers, 25% of breast cancers, 10% of prostate cancers and 5% of pancreatic cancers. The U.S. FDA granted TNG348 Fast Track designation in September 2023. USP1 is an essential enzyme for the survival and proliferation of HRD+ cancer cells.

In preclinical models, TNG348 has strong anti-tumor activity, inducing cell death and tumor growth inhibition in multiple xenograft models. Preclinically, TNG348 has strong synergy with PARP inhibitors in BRCA1/2-mutant or other HRD+ cancer models, as evidenced by marked tumor regressions and the ability to restore sensitivity to PARP inhibition in models of acquired resistance to PARP inhibitors.