LAST WEEK TODAY!

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

Hi, fellow fighters! I’m back on track. This past week was packed with new clinical trial information. I want to highlight the ever-increasing role of AI in drug discovery—we are truly living in a transformative time.

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

Clinical Research

• AAA817 (225Ac-PSMA-617)​
  A Phase II/III clinical trial is set to evaluate the safety and efficacy of AAA817, an Actinium-based therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The Phase II portion, an international, multicenter, open-label study, will gather further data to confirm the appropriate dosing regimen. The Phase III portion will compare the proposed AAA817 dose to the investigator’s choice of standard care treatments in a randomized, open-label, two-arm format.
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• Pocenbrodib​
  An upcoming Phase 1 clinical trial will investigate pocenbrodib hydrochloride as a new treatment option for mCRPC. Developed using AI, the drug targets pathways not addressed by existing therapies. Pocenbrodib functions as a highly selective inhibitor of the CREB-binding protein (CBP) and its homologue p300. By inhibiting CBP/p300, pocenbrodib disrupts some transcriptional processes, potentially impeding cancer cell proliferation and survival.The study will first determine the optimal dose, followed by further exploration as a standalone therapy and in combination with agents such as abiraterone acetate, olaparib, and 177Lu-PSMA-617.
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• IPH4502​
  This Phase 1 trial is examining IPH4502, an antibody-drug conjugate (ADC) targeting Nectin-4, in patients with advanced solid tumors. The trial includes a dose-escalation phase to identify safe and effective dosing levels. Nectin-4’s expression in prostate cancerÂmakes it a candidate for this therapy, making this trial a significant step in testing the ADC’s potential efficacy.
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• Evofosfamide with Immune Checkpoint Inhibitors​
  A Phase 1/2 trial is investigating the combination of evofosfamide, a hypoxia-activated drug, with immune checkpoint inhibitors zalifrelimab and balstilimab in advanced cancers. Evofosfamide is designed to target and disrupt hypoxic regions within the tumor microenvironment, areas often associated with poor T-cell penetration and immunosuppressive signaling. By doing so, it aims to enhance the effectiveness of immune checkpoint inhibitors, potentially overcoming resistance in otherwise treatment-refractory tumors.
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• NDV-GT​
  A recent small trial in China tested a genetically engineered Newcastle disease virus (NDV-GT) in patients with various advanced cancers.The treatment involved weekly infusions over two to three months. Nearly all the 23 participants experienced either tumor shrinkage or halted growth, highlighting the promise of oncolytic virus therapy.
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• Bad News for LAVA-1207Â​
  The Phase 1/2a trial for LAVA-1207, a gamma-delta T-cell engager targeting PSMA-positive tumors, was discontinued after failing to meet internal benchmarks for continued development. Despite this, the drug had shown encouraging signals and met safety standards. Patients who were already responding to the treatment will continue to receive it.

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Preclinical Research

• AI in Drug Discovery Gets Bigger​
  Google’s Isomorphic Labs has developed an AI-driven drug poised to enter clinical trials, aiming to speed up discovery and reduce costs. Using advanced computational methods, the approach identifies promising candidates, predicts interactions, and models outcomes efficiently.
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• Repurposing Antipsychotic Drugs​
  Certain antipsychotic drugs—such as haloperidol, trifluoperazine, and chlorpromazine—are being studied for anti-cancer properties. Preclinical research suggests these medications can induce apoptosis, autophagy, and cell cycle arrest, showing potential as novel treatments for some cancers.
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• A study in Nature Medicine explores using digoxin, a heart medication, to break apart circulating tumor cell clusters that drive metastasis. In a small trial, digoxin reduced cluster size by 2.2 cells on average, a meaningful reduction since these clusters typically consist of only a few cells, potentially lowering the risk of metastases. The drug blocks sodium-potassium pumps on tumor cells, causing calcium uptake that weakens cell bonds and disrupts clusters. Researchers are now working on new, digoxin-inspired molecules and expanding this approach to other cancers, including prostate, pancreatic, and colorectal.
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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