Mark C. Markowski, MD, PhD, an assistant professor of Oncology at Johns Hopkins Medicine, discusses the evaluation of sabizabulin (VERU-111) in a phase 1b/2 trial (NCT03752099) in metastatic castration-resistant prostate cancer (mCRPC). 

The phase 1b/2 trial was conducted to determine a maximum tolerated dose and evaluate for preliminary efficacy in men with mCRPC resistant to androgen receptor (AR)–targeting agents.

A dose-escalation design comprised the phase 1 portion of the trial, and it enrolled patients who had previously received 1 prior AR therapy and up to 1 prior therapy with a taxane, Markowski says. Intrapatient dose escalation was permitted, and patients started with a low dose of sabizabulin administered once per day on a 1 week on, 2 weeks off schedule, Markowski explains. Patients who tolerated that dosing schedule moved to a 2 weeks on, 1 week off schedule, and patients who continued to do well moved to daily dosing, Markowski adds.

Investigators established 63 mg of sabizabulin per day, given continuously, as the recommended phase 2 dose. Though a maximum tolerated dose was not reached, the preliminary efficacy observed at the 63 mg dose prompted investigators to move to phase 2 at that level, Markowski continuous. The phase 2 study evaluated a similar patient population as phase 1, though prior chemotherapy was not permitted, and this portion of the trial evaluated prostate-specific antigen response rates and progression-free survival, Markowski concludes.

Videos

Mark C. Markowski, MD, PhD, discusses the evaluation of sabizabulin in a phase 1b/2 trial in metastatic castration-resistant prostate cancer. 


Dr. Markowski on the Evaluation of Sabizabulin in mCRPC

Mark C. Markowski, MD, PhD, assistant professor, Oncology, Johns Hopkins Medicine, discusses the safety and efficacy of sabizabulin (VERU-111) in a phase 1b/2 trial (NCT03752099) in metastatic castration-resistant prostate cancer (mCRPC).

The study was conducted to establish the maximum tolerated dose and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents.

Efficacy data showed sabizabulin achieved objective response rates between 20% and 30%, Markowski says. However, the most impressive finding was a median progression-free survival of more than 9 months, and some patients have demonstrated disease control after being on the trial for multiple years, Markowski explains. Along with observing preliminary tumor shrinkage, the durable disease control responses are benefiting patients, Markowski adds.

In terms of adverse effects, some grade 1 and 2 toxicities were seen, including fatigue and diarrhea, Markowski continues. While most toxicities were low grade, a couple instances of grade 3 toxicities, including diarrhea, were reported, though those were solved with dose interruption or dose reduction, Markowski adds. Notably, instances of cytopenia or neutropenia, which are common with taxane chemotherapy, were not observed with sabizabulin, Markowski concludes.

Mark C. Markowski, MD, PhD, discusses the safety and efficacy of sabizabulin in a phase 1b/2 trial in metastatic castration-resistant prostate cancer.


Dr. Markowski on the Efficacy of Sabizabulin in Prostate Cancer

Mark Christopher Markowski, MD, PhD, an assistant professor of oncology, and a medical oncologist at the Kimmel Cancer Center, Sibley Memorial Hospital, discusses the safety and efficacy of VERU-111 in patients with metastatic castration-resistant prostate cancer (mCRPC).

One of the most important aspects of the phase 1b/2 clinical trial examining the VERU-111 was its safety profile, according to Markowski. As the agent is a microtubular polymerization inhibitor, it was important to understand its safety profile vs taxane chemotherapy, he added. VERU-111 is an oral, targeted compound that is not quite a cytotoxic chemotherapy agent.

The drug was found to be safe and well tolerated, with most adverse effects being gastrointestinal, including nausea and diarrhea, the majority of which were low grade and manageable with oral medications, or by stopping treatment, Markowski explained.

Moreover, the phase 2 portion of the study yielded promising clinical responses, including objective responses in 44.4% of patients, as well as durable disease stability. The results were surprising, because while patients did not experience a notable decrease in tumor volume, they also did not develop disease progression, and have been on the study for a long time, Markowski said.

Two patients from the phase 1 portion of the study have been on treatment for more than 2 years. In addition to seeing prostate-specific antigen decreases and objective responses, investigators also observed disease stability, Markowski concludes.

Mark Christopher Markowski, MD, PhD, discusses the safety and efficacy of VERU-111 in patients with metastatic castration-resistant prostate cancer.

Mark Christopher Markowski, MD, PhD

Articles

Dr. Markowski on the Evaluation of Sabizabulin in mCRPC

Dr. Markowski on the Efficacy of Sabizabulin in Prostate Cancer

Dr. Markowski on the Safety and Efficacy of VERU-111 in mCRPC