For a phase Ib/II study, researchers looked at the safety and efficacy of ribociclib plus docetaxel (mCRPC) for metastatic castration-resistant prostate cancer. Patients had mCRPC that had not been treated with chemotherapy and progressed on more than equal to 1 androgen receptor signaling inhibitor (ARSI). The primary endpoint of phase II was 6-month radiographic progression-free survival (rPFS) rate, with an alternative hypothesis of 55% versus 35% historical control. Circular tumor cells (CTC) were collected and genomically profiled at the outset. A total of 43 patients were enrolled (N=30 in phase II). There were 2 dose-limiting toxicities observed (grade 4 neutropenia and febrile neutropenia). The recommended phase II dose was docetaxel 60 mg/m2  every 21 days, plus ribociclib 400 mg/day on days 1–4 and 8–15, with filgrastim on days 5–7 and schedule. The most common grade, more than equal to 3 adverse events at the RP2D was neutropenia (37%); however, no cases of febrile neutropenia were observed. The primary endpoint was met; the 6-month rPFS rate was 65.8% [95% CI: 50.6% –85.5%; P=0.005], and the median rPFS was 8.1 months (95% CI: 6.0–10.0 months). A PSA50 response was achieved by 32% of evaluable patients. MYC that was not amplified in baseline CTCs was associated with a longer rPFS (P=0.052). In ARSI-pretreated mCRPC, the combination of intermittent ribociclib plus every 3 weeks docetaxel demonstrated acceptable toxicity and encouraging efficacy. CTC genomic profiling may enrich those who were most likely to benefit. A randomized clinical trial was required for further investigation.