LAST WEEK TODAY!

A summary of what was published on ProstateWarriors.com during the past week

Hi, fellow fighters! This past week has brought encouraging news on both the clinical and preclinical research fronts. Let’s dive into the newsletter and keep fighting on!

As usual, we also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• Phase 1 Clinical Trial for ADRX-0405: This trial is evaluating the safety and efficacy of ADRX-0405, an antibody-drug conjugate (ADC), designed to target the STEAP1 protein, which is highly expressed in prostate cancer and certain other cancers. The trial includes a dose escalation and a dose expansion part, with initial results anticipated in the fourth quarter of 2025. ADRX-0405 has a high drug payload per antibody and has demonstrated significant efficacy in preclinical models.
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• Phase 1 Trial for ASP1002: A bispecific antibody, ASP1002, is being evaluated in a Phase 1 clinical trial. This antibody targets Claudin 4 (CLDN4), a protein overexpressed in various cancers including advanced prostate cancer, and CD137 (4-1BB) on T cells, aiming to stimulate an antitumor immune response. The trial is determining the safety, tolerability, and optimal dosing of ASP1002 in patients with advanced solid tumors, including prostate cancer.
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• Phase 1 Trial of a Polynucleotide Kinase/Phosphatase (PNKP) Inhibitor: A Phase 1 clinical trial for a new PNKP inhibitor is scheduled to begin in 2025. PNKP is an enzyme involved in DNA repair; inhibiting it may make cancer cells more susceptible to treatments like radiation and chemotherapy, especially in tumors with ATM and BRCA mutations.​
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• Phase 2 Adaptive ADT and Docetaxel Trial for mCSPC: This Phase 2 trial is building on an earlier Phase 1b trial by adding docetaxel to an adaptive androgen deprivation therapy (ADT) regimen. The trial uses PSA responses to guide treatment and aims to prolong the castration-sensitive phase of stage IV prostate cancer. The approach includes LHRH analogs, androgen receptor signal inhibitors (ARSIs), and docetaxel, with a focus on optimizing efficacy and tolerability.
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• WOMBAT Trial: This Phase 2 trial is investigating bipolar androgen therapy (BAT) in men with M0 castration-resistant prostate cancer (CRPC) who have rising PSA levels despite darolutamide treatment. The primary goal is to assess whether BAT can extend metastasis-free survival (MFS). This study will also evaluate the safety and tolerability of BAT combined with darolutamide, quality of life, PSA response rates, time to PSA progression, and other markers. The trial is actively recruiting in New South Wales, Australia.
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• Real-World Effectiveness of Apalutamide in mHSPC: A real-world study analyzed the effectiveness of apalutamide (APA) combined with androgen-deprivation therapy (ADT) in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Results indicate that APA+ADT leads to better outcomes than enzalutamide (ENZ)+ADT, abiraterone acetate (AAP)+ADT, and ADT alone. However, this study does not include a direct comparison with darolutamide (DARO).

Preclinical Research

• Evexomostat Research: A $1.2 million grant was awarded to SynDevRx, Inc. for research on their MetAP2 inhibitor drug, evexomostat, in the treatment of aggressive variant prostate cancer (AVPC). This research aims to expand on pre-clinical data showing evexomostat’s efficacy in AVPC models and to identify its specific effects within the AVPC context. Evexomostat is a drug conjugate that binds to the MetAP2 enzyme, triggering a cascade of effects including anti-angiogenesis and cell cycle arrest. Evexomostat is also already being clinically tested in breast cancer patients.
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• NXP800 Research: Research shows that NXP800 targets the Heat Shock Factor 1 (HSF1) pathway, which controls the production of heat shock proteins. Higher levels of heat shock proteins are associated with worse outcomes in prostate cancer. NXP800 has been shown to slow the growth of prostate cancer cells, including those resistant to enzalutamide, in lab and mouse models. The drug modulates the unfolded protein response and impacts other protein molecules that control gene activity.
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• AI Predicting Outcomes in Advanced Prostate Cancer: A study using artificial intelligence (AI) to analyze prostate cancer tissue samples has developed a system called a multimodal artificial intelligence (MMAI) biomarker to predict outcomes for men with metastatic hormone-sensitive prostate cancer (mHSPC). The AI tool uses digital images of tissue samples combined with clinical data, and divides patients into risk groups to predict overall survival, disease progression, and castration-resistant prostate cancer (CRPC).
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• Drug Repurposing Against Metastasis: Researchers have identified 177 genes that appear to drive or restrain metastasis across multiple cancer types. Among these, SP1 appears to promote metastasis, while KLF5 seems to inhibit it. This research suggests a “pan-cancer” mechanism for metastatic progression. The study also highlighted the potential of repurposing existing drugs like Vorinostat to block metastasis.
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• Radiotherapy in High-Burden mHSPC: Research suggests that local interventions, including radiotherapy (RT) to the primary tumor, can benefit patients with metastatic hormone-sensitive prostate cancer (mHSPC), even with a high burden of disease. The rationale includes the “seed-and-soil” theory and synergistic effects of combining RT with hormonal therapies and next-generation androgen receptor inhibitors. Trials like STAMPEDE, HORRAD, and PEACE-1 have shown that RT can improve failure-free survival, reduce local complications, delay castration resistance, and alleviate symptoms.
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And…that’s all folks! For today at least!
Please let me know if there is anything I can improve in my newsletters, and let me know if you have enjoyed the podcast.

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Have a great weekend!

Max