Sabizabulin for Metastatic Castration-Resistant Prostate Cancer

EP: 1.First-Line Therapy Options in Metastatic Castration-Resistant Prostate Cancer

EP: 2.Second-Line Therapy Options in Metastatic Castration-Resistant Prostate Cancer

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EP: 3.Sabizabulin for Metastatic Castration-Resistant Prostate Cancer

EP: 4.Emerging Therapies for Metastatic Castration-Resistant Prostate Cancer

Robert Dreicer, MD: Among the drugs that are in trials now, there is a drug that I have been asked about as I have a relationship with the ongoing phase 3 [trial] and that’s sabizabulin, which is an oral cytoskeletal disruptor. It probably disrupts the cytoskeleton in a number of different mechanisms. It’s not taxane; it’s not a taxane-like drug, although it has similar targets. This oral agent has been in phase 1/2 trials. We have data from a phase 1B study that was led by Dr Mark Markowski of Johns Hopkins Hospital [Baltimore, MD] and this data was presented at ASCO [American Society of Clinical Oncology annual meeting] last year and no doubt will likely be updated at coming meetings. What we know about this agent is it’s an oral agent and it’s relatively well tolerated. Its toxicities tend to be GI [gastrointestinal], nausea, and some diarrhea but at the dose being studied in phase 3, it is a relatively well-tolerated therapy. What we've seen so far in this phase 1B study, which was about 30 patients with mCRPC [metastatic castration-resistant prostate cancer] that had progressed on at least 1 ARI [alpha reductase inhibitor] is that there's some evidence of antitumor activity that’s manifested both in seeing some soft tissue responses, some PSA [prostate-specific antigen] declines, and a couple of these patients have been on a drug for a long period of time, more than a year, approaching 2 years. My perspective on this agent is that there’s activity, it strikes me as almost a static agent, again that’s me speaking, that’s not data that we have yet, but in terms of the ability to have a drug on-board and have the ability to alter the natural history. We’re not seeing a dramatic resolution of disease, but we are seeing people who are able to tolerate this agent for prolonged periods of time and have antitumor activity. It’s an interesting compound because of the data seen to date. There is an ongoing phase 3 trial to test this drug further.

Sabizabulin is in a phase 3 trial entitled VERACITY, and this is a relatively small phase 3 trial that is randomizing patients to receive sabizabulin vs the alternative ARI. Eligibility, mCRPC patients who’ve progressed on an ARI, only minimal taxane prior exposure was allowed, so standard therapy in the castrate-sensitive or metastatic CRPC setting is not allowed, so this is really an early study of ARI progressing patients. The primary end point in this trial; radiographic progression-free survival. The eligibility is otherwise relatively straightforward, encompassing the issue of prior treatment. This study is open at a number of sites both in the U.S. and in Europe, and hopefully, it’s going to accrue relatively rapidly and give us an understanding of the utility of sabizabulin in mCRPC.

If sabizabulin happens to demonstrate activity, meaning meeting its primary end point of radiographic progression-free survival, and would eventually receive regulatory approval, this is a drug that you could also perceive to be used relatively early on in the disease course. It’s being tested in patients who have not been particularly heavily treated, these are ARI progressors, and so these patients are not uncommon. It appears to be a relatively well-tolerated drug, given the fact that there are a number of patients in the early phase 1 studies that have tolerated the drug for long periods of time with disease control. You could see this agent being used exactly in the clinical setting in which it’s being tested, as a drug that may provide long-term disease control with a relatively good quality of life. Now, obviously, we’re not there yet. We need to see. We need to finish phase 3, get the data, and then assess the safety, but this is a drug that you could see being used relatively early in the disease course among a number of clinicians—medical oncologists, urologists— who manage advanced disease and that population of clinicians.

Transcript edited for clarity.