615MO showed early clinical trial data of the microtubule polymerization inhibitor VERU-111. Microtubule targeting is a mainstay of advanced prostate cancer treatment, as microtubule depolymerization inhibitors (taxanes) are approved in both metastatic castration-sensitive and castration-resistant disease. VERU-111 binds at the colchicine binding site to prevent tubulin assembly and is not a substrate for multidrug resistance proteins. VERU-111 has strong preclinical data supporting its efficacy in model systems. In the presented phase 1b study, the safety profile of VERU-111 was comparable to that of cabazitaxel, as shown in the slide below.
The efficacy data presented were limited, and more data will be forthcoming from the phase 2 study that is ongoing.
Dr. Alimonti then discussed abstract 616MO of a novel immunotherapy combination treatment utilizing a vaccine against brachyury, a bidirectional blocker of PD-L1 activation, and TGFbeta signaling, and an IL-15 agonist to promote the expansion of T-cell and NK-cells (but not Tregs). This is an interesting trial, as, beyond the dendritic cell vaccine sipuleucel-T, immunotherapy has shown relatively modest efficacy in prostate cancer. This has been attributed to the presence of immunosuppressive cells in the tumor microenvironment, low mutational burden, and low numbers of tumor infiltrating lymphocytes.
The preliminary results presented are intriguing, with a PSA response rate of 55% (> 30% PSA decline) and two radiographic responses. More patient data is required to adequately assess this therapy, which should be forthcoming per the authors.
Presented by: Andrea Alimonti, MD, Professor of Oncology ETH and Institute of Oncology, Bellizona, Switzerland
Written by: Alok Tewari, MD, PhD, Medical Oncologist at the Dana-Farber Cancer Institute, at the 2020 European Society for Medical Oncology Virtual Congress (#ESMO20), September 19th-September 21st, 2020.
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ESMO Virtual Congress 2020: Novel, Oral Tubulin Inhibitor, in Men with Metastatic Castration Resistant Prostate Cancer (mCRPC) Who Failed an Androgen Blocking Agent: Phase Ib/II Study of VERU-111
ESMO Virtual Congress 2020: Efficacy of BN-Brachyury (BNVax) + Bintrafusp Alfa (BA) + N-803 in Castration-Resistant Prostate Cancer: Results From a Preliminary Analysis of the Quick Efficacy Seeking Trial (QuEST1)