Discussion
HRR, TALAPRO-2, TEAEs, anemia, PRP-002) malignancies, HRR alterations, mCRPC
DISEASE, ADVANCED CANCER, SOLID TUMORS, ANEMIA, CASTRATION-SENSITIVE PROSTATE CANCER
In this phase 1 study of Chinese patients with advanced solid tumors, talazoparib was absorbed rapidly and steady state was generally reached by Day 21, which is consistent with the PK profile previously established in Western and Asian patients (Supplementary Table In a recent 2-part phase 1 study of talazoparib monotherapy in 9 Japanese patients with locally advanced or metastatic solid tumors, Naito et al reported that the single dose CIn addition to the above-mentioned cross study comparison, a modeling approach also supported comparable PK profiles among Asian and Western populations. In an analysis from 2020, Yu et al developed a population PK model based on the data from four clinical trials investigating talazoparib monotherapy in patients with advanced cancers. The analysis included two phase 1 trials (PRP-001 and PRP-002), the phase 2 ABRAZO trial, and the phase 3 EMBRACA trial. Patients had both solid (PRP-001, ABRAZO, and EMBRACA) and hematologic (PRP-002) malignancies [We report that TEAEs with talazoparib monotherapy were generally manageable in Chinese patients with no unexpected safety findings. Most (86.7%) patients experienced treatment-related TEAEs, the majority of which were grade 1–2. One-third of patients experienced grade 3–4 treatment-related AEs and no grade 5 TEAEs were reported. This is consistent with observations by Kotani et al in Japanese patients with solid tumors treated with talazoparib monotherapy, in which all patients experienced treatment-related AEs, 52.6% (10/19) of patients experienced grade 3–4 treatment-related AEs, and there were no grade 5 AEs [The most common total grade 3–4 AEs in our study were hematologic, including treatment-related anemia (20% [3/15]), decreased neutrophil count (20% [3/15]), and decreased platelet count (20% [3/15]). Hematologic AEs are a known class effect of PARP inhibitors, and similar to results seen in Asian and Western patient populations [Our study involved molecularly unselected Chinese patients with advanced solid tumors. The disease control rate was 45.5% (95% CI: 16.7–76.6). This is consistent with findings reported from the first part of the phase 1 study reported by Naito et al of talazoparib monotherapy in a population of molecularly unselected Japanese patients with solid tumors. In the Naito et al study, the overall disease control rate was 44.4% and included 2 patients with stable disease [In conclusion, talazoparib monotherapy in Chinese patients with advanced solid tumors showed no new safety signals. The PK profile was similar to reports from other non-Chinese populations supporting the established 1 mg QD dosing. Our findings support the conclusion that the safety and PK profiles of talazoparib are consistent between populations. This study also provides supportive data for the continued evaluation of talazoparib combined with enzalutamide in Chinese patients in global clinical trials, including TALAPRO-2 (mCRPC unselected for HRR alterations; NCT03395197) and TALAPRO-3 (castration-sensitive prostate cancer with HRR alterations; NCT04821622) [