LAST WEEK TODAY!

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

Hi fellow warriors! Another week of promising clinical and preclinical trials. And I’m letting you know that, at your suggestion, I’m working on a mega table of all the clinical trials I’ve discussed, so you’ll have a quick reference for what’s happening in the world of prostate cancer research. 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.

Clinical Research

• Phase 3 Study of Pasritamig Plus Docetaxel
  ​The ongoing phase 3 KLK2-PASenger trial is investigating pasritamig combined with docetaxel chemotherapy for metastatic prostate cancer. Pasritamig is a bispecific T-cell engager that targets human kallikrein 2 (KLK2), a protein often retained in advanced prostate cancer tissue. The drug works by directing T cells to KLK2-expressing tumor cells, thereby engaging the immune system. This combination approach is supported by the rationale that docetaxel may modify the tumor immune environment, increasing T-cell activity and making the cancer more vulnerable to immune therapy. Preclinical evidence also suggests that combining chemotherapy and T-cell engagers enhances the visibility and vulnerability of tumor cells to immune attack. Earlier Phase 1 studies of pasritamig alone in men with metastatic castration-resistant prostate cancer (mCRPC) showed that over 40% of participants achieved a reduction in PSA of at least 50%.​
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• Phase 1b/II Trial of AMO959, Pluvicto, and ARPIs
  ​An ongoing phase Ib/II trial is exploring a triple combination therapy for metastatic castration-resistant prostate cancer (mCRPC) that involves AMO959, Pluvicto (lutetium-177 vipivotide tetraxetan), and androgen receptor pathway inhibitors (ARPIs). Pluvicto is an established radioligand therapy that targets PSMA-positive cancer cells, delivering beta radiation directly to the tumor. AMO959 is an experimental, oral medicine that acts as a direct activator of AMPK, a metabolic regulator designed to disrupt cancer cell metabolism and inhibit androgen receptor function. The ARPIs, such as abiraterone or enzalutamide, provide continued hormonal blockade. This strategy is designed to overcome mCRPC resistance by combining metabolic targeting, targeted radiation, and hormonal suppression.​
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• Phase 2 Trial of Pacritinib (POSTPONE)
  ​The phase 2 POSTPONE trial is a highly personalized study investigating pacritinib, a potent JAK2/IRAK1 inhibitor, for advanced prostate cancer. Enrollment in this trial is restricted to patients whose tumor metastases are strongly positive for STAT5 activation, specifically requiring detectable nuclear STAT5 in over 5% of cancer cells confirmed via a recent tumor biopsy. This specialized entry criterion is based on findings showing that the JAK2-STAT5 pathway is a critical mechanism of resistance to androgen receptor signaling inhibitors (ARSI) in mCRPC. Pacritinib aims to selectively disrupt this resistance axis, as preliminary data suggests that JAK2-STAT5 blockade induces apoptosis in prostate cancer models that survive ARSI therapy.​
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Preclinical Research & Reviews

• Dr. Sartor Explained the ARTISAN Trial
  ​Dr. Oliver Sartor presented information on Lead-212 (Pb-212), which is being studied in the ARTISAN (AB001) trial as a significant advance in precision radioligand therapy for metastatic castration-resistant prostate cancer. Lead-212, which is still in early clinical evaluation, is an alpha-emitting radiopharmaceutical known for its unique profile. Key characteristics include an extremely short radiation path length, allowing for highly localized energy delivery with minimal damage to surrounding healthy tissues, and a short half-life of just 10.6 hours. This short exposure window may allow healthy cells, such as bone marrow and immune cells, to recover more quickly than with longer-lived isotopes, potentially reducing marrow toxicity. The rapid decay also supports flexible treatment scheduling, possibly enabling multiple doses within weeks.​
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• CBPD-409: An Oral PROTAC Degrader
  CBPD‑409 is an experimental, oral medicine utilizing a strategy known as PROTAC degradation to target two helper proteins, CBP and p300, which advanced, treatment-resistant prostate tumors rely on to activate cancer-driving genes. CBP and p300 work in partnership with the androgen receptor (AR), the main signal fueling most prostate cancers. By tagging these proteins for destruction, CBPD-409 is designed to dismantle the cancer’s control centers (enhancers) more completely than older inhibitor drugs. Preclinical work showed that CBPD‑409 effectively degraded CBP/p300 and demonstrated stronger tumor growth control in animal studies compared to older inhibitors (like CCS1477 or GNE‑049) or enzalutamide used alone. Crucially, its mechanism erases the enhancer signal, which relies on CBP/p300 activity, leading to a more complete quieting of AR-driven genes. The drug exhibited high selectivity, hitting AR-positive prostate cancer cells hard while having minimal effect on AR-negative or neuroendocrine models. Furthermore, CBPD-409 showed encouraging synergy when combined with enzalutamide, leading to deeper tumor control in resistant models, including tumor regressions in more than half of animals.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max