Sabizabulin was well tolerated and associated with significant and durable objective tumor responses in patients with metastatic castration resistant prostate cancer.
Sabizabulin (VERU-111) was well tolerated and associated with significant and durable objective tumor responses in patients with metastatic castration resistant prostate cancer (mCRPC), according to phase 1b/2 clinical trial (NCT03752099) results presented at the 2021 ESMO Congress.
Both phases of the study consisted of patients who were previously treated with at least 1 androgen receptor-targeted therapy. The aim of the study was to evaluate the safety, maximum tolerated dose, and efficacy of sabizabulin.
Patients included in the study were advanced in their treatment, Mark C. Markowski, MD, PhD, medical oncologist from John Hopkins University in Baltimore, Maryland, highlighted during his presentation. Many patients had previously been treated with abiraterone acetate (Zytiga), enzalutamide (Xtandi), a combination of both, or apalutamide (Erleada) or proxalutamide.
The phase 1b portion used a 3+3 design in 39 patients (median age, 74 years). Initially, each dose was administered orally on days 1-7 on a regimen of every 21 days. If this regimen was well tolerated and considered safe, the frequency was increased to a daily dosing on days 1-14 every 21 days. And if that was tolerated, patients then advanced to dosing daily until disease progression or toxicity.
In the phase 1b portion of the study, 10 patients reached at least 4 cycles of continuous dosing. Of that 10, 6 had any PSA response, 2 had at least a 50% PSA response. Additionally, two patients had a partial response, with the remaining 8 achieving stable disease. The median radiographic progression-free survival (rPFS) was greater than 12 months (range, 6.0-28+ months). And as of August 2021, 2 of the 10 patients remained on the study.
“That’s the most mature data we have. (It’s) a bit difficult given our dose escalation strategy,” Markowski noted.
The open-label phase 2 portion of the study comprised 44 patients (median age, 73 years) and evaluated the recommended dose of 63 milligrams (mg) daily. “We found that (the) recommended phase 2 dose was 63 milligrams per day, so daily dosing was safe and feasible,” Markowski explained.
The most common adverse events among 54 patients included diarrhea, fatigue, ALT and AST increases, all of which were mostly grade 1 and 2. Markowski added that there were no reports of clinically relevant neutropenia or neurotoxicity, “which we’ve seen before with taxane chemotherapy.”
Objective response rate in the intention-to-treat population (n = 26) was 20.7%, with 5 partial responses and 1 complete response. And in evaluable patients who qualified for a future phase 3 trial (n = 26) it was 23.1%.
In patients that received at least 63 mg (n = 55) median rPFS is estimated to be at least 7.4 months.
Markowski detailed that a phase 3 trial, known as VERACITY (NCT04844749), is currently underway and is evaluating 32 mg of sabizabulin for the treatment of mCRPC against an alternative AR-targeting agent. Patients in this study had prior treatment with 1 AR-targeted therapy, and no chemotherapy. This trial has a primary endpoint of rPFS.