Study design and patients
toxicity, toxicities, death
ONCOLOGY, DISEASE PROGRESSION, SOLID TUMORS, DRUG-DRUG INTERACTION
Patients (aged ≥18 years) had locally advanced or metastatic solid tumors resistant to standard therapy, or for which no standard therapy had been available, as well as a baseline Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 or 1. To be included, all patients were required to have adequate bone marrow, renal, and liver function. Additional inclusion and exclusion criteria are listed in Supplementary Table Prior clinical studies have demonstrated the maximum tolerated dose of talazoparib monotherapy to be 1 mg QD in Western and Japanese patients [A single dose of talazoparib 1 mg was administered orally on Day –9. From Cycle 1 Day 1, patients received talazoparib 1 mg QD orally on a continuous basis at approximately the same time each day (preferably in the morning) until disease progression, death, unacceptable toxicity, or withdrawal of consent. Dose interruptions or reductions were not required unless toxicity persisted at grade 2 for ≥7 days. Daily dosing was paused for grade ≥3 hematologic toxicities. Supportive care including blood products was allowed as appropriate per local guidance. To minimize any drug-drug interaction effects relating to talazoparib exposure and potential alteration to efficacy, co-medication with P-glycoprotein (P-gp) inhibitors and inducers was prohibited for Cycle 1 when intensive PK assessments were scheduled after both single-dose and multiple-dose talazoparib administrations. After Cycle 1, only potent P-gp inhibitors were prohibited to accommodate more co-medication options.The final protocol and any amendments were reviewed and approved by the independent ethics committees at each of the investigational centers participating in the study. This study was conducted in compliance with the ethical principles originating in or derived from the Declaration of Helsinki and in compliance with all International Council for Harmonization Guidelines for Good Clinical Practice. Informed consent was obtained from all individual patients included in the study.