A phase 1b/2 study of intermittent talazoparib plus temozolomide in patients with metastatic castration-resistant prostate cancer and no mutations in DNA damage response genes.

ABSTRACT: As monotherapy, PARP inhibitors have little cytotoxic effect in tumors without homologous recombinant repair (HRR) alterations. Supported by preclinical models, we hypothesized that the PARP inhibitor talazoparib in combination with temozolomide chemotherapy could induce DNA damage leading to cell death and tumor response in patients with metastatic castration-resistant prostate cancer (mCRPC) without HRR alterations. In this phase 1b/2 trial (NCT04019327; registration date July 11, 2019), patients with progressive mCRPC without HRR mutations who failed at least one androgen receptor signaling inhibitor were enrolled in escalating doses of intermittent talazoparib plus temozolomide to determine the maximum tolerated dose and recommended phase 2 dose (RP2D) in Phase 1b. Phase 2 used a compo

SUBMITTER: Autio KA 

PROVIDER: S-EPMC12515242 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature