Pfizer has dosed the first subject in a Phase III TALAPRO-3 clinical trial of oral drug talazoparib plus enzalutamide in men with deoxyribonucleic acid damage response (DDR)-deficient metastatic castration-sensitive prostate cancer (mCSPC).
The first participant was dosed at a study centre in Glendale, California, US.
A poly (ADP-ribose) polymerase (PARP) inhibitor, talazoparib was found to hinder PARP enzyme activity and trap PARP at the DNA damage area, in preclinical studies. The drug thereby reduces the growth of cancer cells and causes cancer cell death.
Marketed as Xtandi, enzalutamide is an androgen receptor inhibitor intended for castration-resistant prostate cancer (CRPC) and mCSPC treatment.
The randomised, double-blind, placebo-controlled, international Phase III TALAPRO-3 trial will assess the efficacy and safety of talazoparib plus enzalutamide against placebo in DDR-deficient mCSPC patients.
It will enrol a total of 550 male subjects at nearly 285 trial centres across 28 countries.
Trial subjects will be given either once-daily doses of 0.5mg talazoparib plus 160mg enzalutamide or placebo along with enzalutamide.
Radiographic progression-free survival (rPFS) will be the trial’s primary goal while overall survival (OS) will form one of the secondary goals.
The company plans to conclude the trial by 2024.
Pfizer Global Product Development Oncology chief development officer Chris Boshoff said: “By combining enzalutamide, which has a proven clinical benefit in men with metastatic castration-sensitive prostate cancer, with talazoparib, our PARP inhibitor that is active in DDR-mutated cancer, we may be able to offer a new treatment option that targets the underlying genetic mechanisms associated with DDR-mutated mCSPC.”
The enzalutamide-talazoparib cocktail is also being analysed in a two-part Phase III TALAPRO-2 trial in male patients with metastatic CRPC with and without DDR defects.
At present, talazoparib has the approval to treat adults with deleterious or suspected deleterious germline BRCA-mutated HER2-negative locally advanced or metastatic breast cancer.
Last week, Pfizer reported that its rheumatoid arthritis drug, tofacitinib, lowered the cumulative occurrence of death or respiratory failure in Covid-19 pneumonia patients, meeting the primary goal of the STOP-COVID study in Brazil.