Early Data in mCRPC Show Promise of Sabizabulin

Article

Durable objective responses coupled with an acceptable safety profile were reported for sabizabulin in patients with metastatic castration-resistant prostate cancer at 2021 ESMO.

Durable antitumor activity was noted with the use of sabizabulin (VERU-111) in patients with metastatic castration-resistant prostate cancer (mCRPC) who were treated in a phase 1b/2 trial (NCT03752099), according to data presented at the 2021 European Society for Medical Oncology Congress.

Sabizabulin was well tolerated and associated with significant and durable objective tumor responses in patients with

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.

Reference

Markowski M, Eisenberger M, Tutrone R, et al. Sabizabulin, an oral cytoskeleton disruptor, to treat men with metastatic castration resistant prostate cancer who failed an androgen receptor targeting agent. Presented at 2021 ESMO Congress; September 16-21, 2021; virtual. 578MO.

Related Videos
Patients with CML can become an active part of their treatment plan by discussing any questions that come to mind with their providers.
Jorge E. Cortes, MD, emphasizes proper communication between patients with chronic myeloid leukemia and their providers during the treatment course.
Dietary interventions or other medications may help mitigate diarrhea in patients who undergo therapy for chronic myeloid leukemia.
Whether CAR T-cell therapy or T-cell engagers should dominate the multiple myeloma landscape may be hard to determine, says David S. Siegel, MD.
Next steps for research in the multiple myeloma space may include the development of novel CAR T-cell strategies and bispecific antibodies.
Ongoing research may clarify the potential benefit of avelumab when administered in combination with other agents in advanced urothelial carcinoma.
Spatial analyses may help determine factors that influence responses to sacituzumab govitecan-containing regimens in urothelial carcinoma.
Adverse effects associated with oral azacitidine in low- or intermediate-risk MDS are typically transient, according to Mikkael A. Sekeres, MD, MS.
Attending educational sessions may help with understanding how to manage toxicities associated with enfortumab vedotin in rare genitourinary cancers.
Ongoing genomic profiling analyses in the ASC4FIRST trial may further determine which patients with CML may benefit from treatment with asciminib.
Related Content