Mark Markowski, MD, PhD, discusses the design of a phase 1B/2 study of sabizabulin in men with metastatic castration-resistant prostate cancer who have had treatment and progression on an androgen receptor–targeting agent.
Mark Markowski, MD, PhD, assistant professor of oncology, at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Oncology, discusses the design of a phase 1B/2 study of sabizabulin (VERU-111) in men with metastatic castration-resistant prostate cancer (mCRPC) who have had treatment and progression on an androgen receptor (AR)–targeting agent.
The trial, which was initially a phase 1 study, consisted of 2 parts and examined the oral cytoskeleton disruptor, sabizabulin. The dose escalation portion of the study used a 3+3 design and enrolled a total of 40 patients with mCRPC treated with at least 1 AR–targeting agents who received daily oral doses of 4.5–81 mg with the goal of determining the recommended phase 2 dose.
Following this, the phase 2 portion of the study tested a daily dose of 63 mg in patients with no prior chemotherapy. Efficacy was assessed using PCWG3 and RECIST 1.1 criteria, and end points included efficacy, radiographic progression-free survival, and overall response rates.
0:08 | It is a phase 1 study initially. We had a dose escalation study, 40 patients were enrolled, and we allowed men with metastatic castration resistant prostate cancer who have had treatment with at least 1 AR targeted therapy and up to 1 taxane chemotherapy for the phase 1 portion of it. It's a traditional phase 1 study where patients started at a low dose, but we did allow for intrapatient dose-escalation. Patients were initially started at 1 week on 2 weeks off. If they did well, they went up to 2 weeks on, 1 week off, and then eventually daily dosing.
0:43 | As we worked our way through the dose escalation, we determined that 63 mg per day continuously dosed was going to be the recommended phase 2 dose, and we did not identify a maximum tolerated dose, so we went up to 72 mg and began to see a little bit more GI toxicities. We decided to move down to the 63 mg and move that forward.
1:06 | With the phase 2 study, again, that is the 63 mg/day continuously dosed cohort with a similar patient population, but this cohort did not allow for prior chemotherapy. At 63 milligrams, we were looking at efficacy, radiographic progression-free survival and overall response rates.