LAST WEEK TODAY!

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

Hello fellow warriors! From the hottest Italian May I can remember, here’s what’s happening in cancer research and clinical trials.
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: Adding Carboplatin in the CaBRA Study​
  The CaBRA trial investigates a quadruple-intensification therapy that adds carboplatin to a backbone of lifelong ADT, darolutamide, and docetaxel-based chemotherapy. This study specifically targets a high-risk subgroup of patients with metastatic castration-sensitive prostate cancer (mHSPC) who possess BRCA mutations or neuroendocrine differentiation, both of which are linked to aggressive disease and early resistance. The biological rationale is that BRCA mutations make tumor cells more sensitive to platinum-based chemotherapy like carboplatin, while neuroendocrine phenotypes, which often resist standard hormone therapy, may respond better to this more intensive chemotherapy approach.
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• Phase 3 Trial: VECTRA-01 and Alpha-Emitting AZD2265​
  The VECTRA-01 trial is a pivotal study evaluating AZD2265 (²²⁵Ac-PSMA-I&T), a targeted alpha-emitting radioligand therapy for PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). Unlike beta-emitters, alpha radiation delivers higher energy over shorter distances, potentially providing a therapeutic advantage for patients who have already progressed after receiving at least two cycles of beta-emitting radioconjugates. The trial compares AZD2265 against the investigator’s choice of standard care, such as cabazitaxel or an ARPI switch, aiming to establish it as a new treatment option for heavily pre-treated patients.
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• Phase 2 Trial: Encouraging Results for B7-H3 ADC YL201​
  In a study involving 82 heavily pretreated patients with advanced mCRPC, the B7-H3–targeting antibody–drug conjugate YL201 demonstrated notable clinical activity. The trial reported a confirmed PSA50 response rate of 38.5% and a median radiographic progression-free survival of 9.1 months. Activity was particularly strong at a 2.4 mg/kg dose and was maintained in high-risk patients with visceral metastases, including those with liver involvement who typically face poor outcomes with conventional therapies.
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• Phase 2 Trial: The MOMENT Trial and EZH2 Inhibition​
  The MOMENT trial evaluates the oral EZH2 inhibitor mevrometostat in combination with enzalutamide for patients with mCRPC who have progressed on an earlier AR pathway inhibitor but have not yet received abiraterone. By adding an EZH2 inhibitor, the study seeks to “re-discipline” the epigenetic program of the tumor, preventing cancer cells from escaping androgen dependence through lineage plasticity. This trial focuses on a specific real-world treatment window, aiming to delay disease progression before patients exhaust other standard options like PARP or AKT inhibitors.
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• Phase 2 Trial: Zanzalintinib for Difficult-to-Treat Metastases​
  ​Zanzalintinib is a new investigational drug being tested in a single-arm Phase 2 trial for mCRPC patients with soft tissue or visceral metastases. The drug employs a multi-targeted approach by inhibiting VEGFR2 to starve tumors of blood supply while blocking MET, AXL, and MERTK to prevent metastasis and immune suppression. Preclinical data suggests that zanzalintinib may enhance the effectiveness of immunotherapy by converting “cold” tumors into immunologically “hot” ones, which is why it is often studied in combination with checkpoint inhibitors.
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• Phase 1/2 Trial: Epigenetic KAT6 Inhibitor and Darolutamide​
  A Phase 1b/2 trial is planned for late 2026 to test an investigational KAT6 inhibitor combined with darolutamide in patients with mCRPC. This inhibitor blocks the epigenetic enzymes KAT6A/B, which downregulates oncogenic drivers like MYC and impairs tumor cell-cycle progression. By disrupting chromatin accessibility at androgen receptor (AR) target genes, the combination creates a two-pronged attack that simultaneously blocks the receptor and disables the epigenetic machinery supporting treatment resistance.
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Preclinical Research & Reviews

• SIRT1 Identified as a Driver of Neuroendocrine Prostate Cancer​
  Researchers have identified SIRT1 as a critical target in neuroendocrine prostate cancer (NEPC), a highly aggressive subtype that often emerges after hormone therapy fails. Preclinical models showed that increased SIRT1 activity drives the transformation of prostate cancer cells into a neuroendocrine state, while inhibiting it with the compound selisistat slows tumor growth and can reverse these dangerous characteristics. While these findings are currently based on cell and mouse studies, they suggest that SIRT1 inhibition could eventually provide a path for drug repurposing to treat therapy-resistant prostate cancer.
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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