 Mark Markowski, MD, PhD

Mark Markowski, MD, PhD, assistant professor of oncology, at Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Medical Oncology, discusses the results of a phase 1b/2 study (NCT03752099) examining treatment with sabizabulin (VERU-111) in patients with metastatic castration-resistant prostate cancer (mCRPC).

Markowski noted that overall, sabizabulin was found to be safe and only mild toxicities were reported in phase 1 of the trial. Patients primarily had grade 1 or 2 adverse events, including fatigue and GI toxicities.

In the phase 2 portion of the study, some tumor reduction was seen, the overall response rate was in the 20% to 30% range, and the median progression-free survival was between 9-12 months.

 For the phase 1, dose finding study looking at safety, we did find that sabizabulin was pretty safe. It had mild toxicity, grade 1 or 2 primarily, and mostly fatigue and GI toxicities were diarrhea, nausea, and most patients did very well. We had a few grade 3 toxicities in the GI tract. Those were managed well with dose interruption or dose reduction. Again, from the safety perspective, patients did quite well in phase 1.

Then we did see preliminary activity in phase 2. We saw some tumor reduction; we had an objective response rate in the 20% to 30% range. What we found is that patients were on the study for a long time. Progression-free survival was in the range of 9 to 12 months, but we had patients on study for 3 years and they continue on the study. There was some good disease control and in addition to some of the responses in terms of tumor reduction, we saw a lot of disease stability that was durable, so we were happy with it.

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Mark Markowski, MD, PhD, discusses the results of a phase 1b/2 study examining treatment with sabizabulin in patients with metastatic castration-resistant prostate cancer.


Favorable Safety Profile Seen With Sabizabulin in mCRPC

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.

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.

 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.

 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.

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 | Authors

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