Sabizabulin for metastatic castration-resistant prostate cancer clears phase early trial

The oral cytoskeleton disruptor sabizabulin shows antitumour activity in men with metastatic castration-resistant prostate cancer (mCRPC), while having a favourable safety profile, as shown in the results of a phase Ib/II trial.

A total of 39 mCRPC patients treated with one or more androgen receptor–targeting agents were included in the phase Ib segment, which applied a 3+3 design with escalating daily oral doses of 4.5–81 mg and increasing schedule. Prior taxane chemotherapy was permitted. The phase II segment examined a daily dose of 63 mg in 41 patients with no prior chemotherapy.

Researchers assessed efficacy was assessed using the Prostate Cancer Working Group 3 (PCWG3) and Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria.

The maximal tolerated dose (MTD) was not defined in the phase Ib, while the recommended phase II dose was set at 63 mg/day. The most common adverse events (AEs; >10 percent frequency) with the 63 mg oral daily dosing (combined phase Ib/II data) were predominantly grade 1–2 events.

Grade ≥3 events included diarrhoea (7.4 percent), fatigue (5.6 percent), and alanine aminotransferase/aspartate aminotransferase elevations (5.6 percent and 3.7 percent, respectively). None of the patients developed neurotoxicity and neutropaenia.

Preliminary efficacy data was obtained in the group of patients treated with ≥1 continuous cycle of ≥63 mg. Objective response was seen in six out of 29 (20.7 percent) patients with measurable disease (one complete, five partial). Prostate-specific antigen levels declined in 14 out of 48 (29.2 percent) patients.

The Kaplan–Meier median radiographic progression-free survival was 11.4 months (n=55), with durable responses lasting >2.75 years.

The findings support the ongoing phase III VERACITY trial of sabizabulin in men with mCRPC.