LAST WEEK TODAY!

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

Hi fellow warriors! Another week of fighting against our common enemy. And another wave of new weapons.! 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 3 Trial: BNT324 (DB-1311) Antibody-Drug Conjugate for mCRPC
  BNT324 (DB-1311) is a first-in-class antibody-drug conjugate (ADC) targeting B7-H3 that has entered a head-to-head Phase 3 trial against docetaxel for patients with metastatic castration-resistant prostate cancer (mCRPC). In earlier Phase 1/2 results, the drug showed an objective response rate of roughly 42% and achieved disease control in approximately 95% of evaluable patients, even among those who were heavily pretreated. These patients had often failed prior therapies such as PARP inhibitors, lutetium-177 PSMA, and immunotherapy. The treatment appears to have a manageable safety profile.
• Phase 2 Trial: ANDROMEDA Alpha vs. Beta PSMA Therapy
  The ANDROMEDA phase 2 trial is a head-to-head comparison evaluating the efficacy of 1 dose of the alpha-emitting 225Ac-PSMA-617 against 2 doses of the beta-emitting 177Lu-PSMA-617 (Pluvicto) in patients with recurrent oligometastatic prostate cancer. Both therapies are combined with stereotactic body radiotherapy (SBRT) to target visible lesions while addressing microscopic disease spread. Researchers hypothesize that the higher linear energy transfer and shorter range of alpha particles may outperform beta particles in eradicating resistant micrometastases.​
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• Phase 1/2 Trial: PDS01ADC (M9241) and Docetaxel Combination
  ​Preliminary data from a Phase 1/2 trial involving PDS01ADC (an IL-12 immunocytokine) combined with docetaxel shows promising activity in patients with progressive mCRPC. PDS01ADC is designed to recognize DNA-histone epitopes in necrotic tumor regions, a process enhanced by the necrotic effects of docetaxel chemotherapy. Among 16 patients studied, the median progression-free survival reached 9.6 months, and 13 patients experienced a decline in PSA levels.​
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• Phase 1 Trial: Actinium-225 NTSR1-Targeted Radiopharmaceutical SKL35501
  SKL35501 is a next-generation radiopharmaceutical that targets neurotensin receptor 1 (NTSR1), a receptor overexpressed in aggressive prostate tumors, including neuroendocrine prostate cancer (NEPC). This Phase 1 trial utilizes actinium-225, a potent alpha-emitter that delivers high-energy radiation to cause lethal double-strand DNA breaks in cancer cells. Preclinical data indicated that the ligand achieves high tumor uptake with rapid clearance from normal tissues.
• Phase 1 Trial: DCC-2812 Integrated Stress Response Activator
  DCC-2812 is an oral drug currently in Phase 1 testing for advanced cancers, including hormone-therapy-resistant prostate cancer. It functions by activating the GCN2 kinase, which triggers the cell’s integrated stress response (ISR) and pushes cancer cells toward programmed cell death (apoptosis). By allosterically boosting the GCN2 enzyme, the drug slams the brakes on normal protein production while ramping up stress-handling genes like ATF4. In laboratory cancer models, this approach slowed tumor growth by up to 92% as a single agent.​
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Preclinical Research & Reviews

• SHR-A1921: Next-Generation TROP2-Targeted Antibody-Drug Conjugate
  SHR-A1921 is a novel ADC designed to exploit TROP2 overexpression, which is common in metastatic castration-resistant prostate cancer (mCRPC). It utilizes a humanized antibody conjugated to a potent topoisomerase I inhibitor that can kill both target cells and neighboring non-targeted tumor cells through a “bystander effect”. Preclinical studies show the drug effectively kills TROP2-positive prostate cancer cells and shrinks tumors in patient-derived organoids. While early clinical trials have shown promise in other advanced solid tumors, specialized trials for prostate cancer are expected to be the next step.​
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• AlphaGenome AI Tool for DNA Analysis
  AlphaGenome is a new artificial intelligence tool that can read up to a million letters of DNA code to predict gene activity and how DNA folds. This tool is significant for cancer research because it can identify “silent” DNA changes in control switches that fuel tumors, rather than just looking at protein-making parts. It has shown superior accuracy in predicting how DNA changes mess with gene splicing and how far-away DNA switches connect to specific genes. By identifying these tiny tweaks, AlphaGenome helps doctors understand why cancer grows and aids in the selection of targeted drugs.​
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• Nanotech Advancement: LipoNCs@pGSDMB for Bone Pain and Metastasis
  ​A new “neuroimmunotherapy” nanocarrier, LipoNCs@pGSDMB, has been designed to treat bone metastases by activating only in the high-oxidative-stress environment of tumors. It delivers a STING agonist to boost the immune system and a DNA plasmid that causes cancer cells to explode via a process called pyroptosis. Beyond killing tumors, the therapy restores normal calcium channels to block pain signals and halt the crosstalk between tumors and nerves. In animal models, this system achieved 94% tumor shrinkage and rebuilt bone structure while stimulating a systemic immune response.​

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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