LAST WEEK TODAY!

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

Hi fellow warriors! This week we have four interesting clinical trials. Two come directly from China. Effective therapies can come from anywhere in the world! Stay strong and fight on!

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

• Phase 2 trial for EVOLUTION (177Lu‑PSMA‑617 plus Checkpoint Blockade)​
  The Phase II EVOLUTION trial is a randomized study designed to determine if adding the dual checkpoint inhibitors, ipilimumab and nivolumab, improves outcomes when combined with the radioligand therapy 177Lu-PSMA-617 (Pluvicto) in men diagnosed with metastatic castration-resistant prostate cancer (mCRPC). The strategy aims to hit cancer with checkpoint blockade to amplify antitumor immunity, based on the principle that radioligand therapy can modulate the tumor microenvironment and promote immunogenic cell death. Early data presented in 2025 indicated a potentially meaningful benefit for the combination, showing that 33% of patients receiving the combination were free of progression at 12 months,versus 17% of patients who received 177Lu-PSMA-617 alone.
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• Phase 1 trial for RAD 402 (Terbium-Based Radioligand)​
  A first-in-human Phase 1 therapeutic trial of RAD 402 has been approved by the Australian Human Research Ethics Committee for patients with metastatic or locally advanced prostate cancer. RAD 402 is a radioligand that utilizes a KLK3 (PSA)-targeting monoclonal antibody labeled with the isotope terbium-161. The rationale for this agent stems from the fact that KLK3, which encodes Prostate Specific Antigen, is highly expressed in most prostate adenocarcinomas and their metastases.A key element of this program is the choice of terbium-161, which differs from beta-only emitters because it delivers both medium-energy beta particles and low-energy Auger and internal conversion electrons. This dual-emission profile concentrates the lethal dose over very short ranges (nanometer-to-micrometer), which is hypothesized to be advantageous against isolated cancer cells and micrometastases.
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• Phase 2 trial for SHR3680, HS-20093, and SHR2554 Triple Therapy​
  A Phase II study is currently investigating a novel triplet therapy for metastatic prostate cancer that involves SHR3680 (rezvilutamide), HS-20093, and SHR2554, aiming for enhanced outcomes through dual-pathway inhibition. The regimen utilizes SHR3680, a selective androgen receptor (AR) antagonist that has demonstrated significant improvements in survival endpoints compared to earlier agents (enzalutamide) and serves as the backbone hormonal therapy. The combination includes HS-20093, which is a novel antibody-drug conjugate (ADC) targeting the B7-H3 surface protein; this target is selected because androgen deprivation therapy indirectly enhances B7-H3 expression, creating a therapeutic vulnerability for the ADC. The final component is SHR2554, an oral inhibitor of EZH2(Enhancer of Zeste Homolog 2), an epigenetic regulator whose inhibition can help reverse resistance mechanisms, restore sensitivity to hormonal therapies, and impede aggressive tumor phenotypes, such as neuroendocrine differentiation.
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• Phase 3 trial for Rezvilutamide vs. Enzalutamide in mHSPC​
  A new Phase 3 clinical trial is preparing to recruit patients with metastatic hormone-sensitive prostate cancer (mHSPC) to conduct a head-to-head comparison between two leading oral androgen receptor antagonists: rezvilutamide (SHR3680)versus enzalutamide. This trial represents an important evolution in treatment research by directly evaluating the efficacy and safety of these agents when combined with androgen deprivation therapy in the hormone-sensitive setting. Rezvilutamide is a next-generation AR blocker designed to minimize penetration into the brain, potentially reducing neurologic side effects like seizures and fatigue that are associated with enzalutamide. Earlier data has indicated rezvilutamide has promising clinical outcomes, including a 42% reduction in mortality risk relative to older treatment standards. The randomized trial aims to refine therapeutic choice by comparing progression-free survival, overall survival, and patient-reported quality of life and side-effect profiles.
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Preclinical Research & Reviews

• DeepTarget Computational Framework for Mechanism Discovery​
  DeepTarget is a new computational framework developed by researchers at Sanford Burnham Prebys and collaborators that maps both direct and indirect anti-cancer mechanisms across diverse cellular contexts, based on the reality that small-molecule drugs rarely act through only a single target. The framework operates on the fundamental premise that if knocking out a gene using CRISPR mimics the cellular response to a drug, that gene is likely part of the drug’s pathway or target. DeepTarget integrates large-scale drug viability screens, genome-wide CRISPR knockout data, and matched omics profiles to identify primary targets, context-specific secondary targets, and mutation-specific preferences governing drug responses. This approach allows DeepTarget to uncover pathway and context effects often missed by traditional “on-target/off-target” labels, which has proven successful, as it outperformed recent structure-oriented tools in 7 of 8 curated gold-standard benchmarks.

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