LAST WEEK TODAY!

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

Hi fellow warriors! This is AACR 2025 week, and there’s a lot to talk about regarding new treatments for solid tumors that could potentially include prostate cancer. Studies directly focused on prostate cancer have not yet been fully revealed, but I’ve already managed to summarize a few things. Enjoy the read! 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

• BA1106​
  BA1106 is China’s first anti-CD25 monoclonal antibody to enter clinical trials for advanced solid tumors. CD25, found on immunosuppressive regulatory T cells (Tregs), is linked to poor prognosis in prostate cancer. BA1106 selectively depletes Tregs through antibody-dependent cellular cytotoxicity (ADCC) without blocking IL-2 signaling, preserving beneficial CD8+, CD4+, and natural killer (NK) cell functions. In a Phase I trial involving 31 patients with refractory or metastatic tumors, BA1106 was well-tolerated, with mostly mild side effects. A 34.6% disease control rate (stable disease) was achieved, suggesting promise for prostate cancer, although specific results in this cancer type were not detailed.
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• Grape Seed Extract (GSE)​
  GSE, a natural phytochemical known for its tolerability, was studied as an intervention for men with biochemical recurrence(rising PSA after local treatment) to delay the need for androgen deprivation therapy (ADT). A Phase II trial found that GSE (150 mg orally twice daily for 12 months) significantly slowed PSA progression. Average PSA doubling time (PSADT) increased from 5.71 to 6.86 months, with 78% of participants experiencing some PSADT lengthening and 37% achieving a 30% or greater improvement. GSE was well-tolerated, with minimal side effects. Larger, placebo-controlled studies are needed to confirm these findings.
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• 5T4-Targeted ADCs​
  Next-generation ADCs targeting the 5T4 antigen are advancing prostate cancer therapy, especially in metastatic castration-resistant prostate cancer (mCRPC), where 5T4 expression is elevated. This ADC, currently in Phase I trial, links an IgG1 antibody to exatecan (a topoisomerase I inhibitor) via a cleavable linker, ensuring precise drug delivery and minimal off-target effects. Advanced conjugation technologies enhance the drug’s stability, allowing higher doses. Combining 5T4-ADCs with immune-stimulating payloads could further strengthen anti-tumor immunity, offering new hope for patients with advanced prostate cancer.
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• Nezastomig (REGN5678) + Cemiplimab​
  This combination therapy is being tested for mCRPC. Nezastomig is a bispecific antibody, and cemiplimab is an immune checkpoint inhibitor. In a Phase 1/2 trial 78 men with heavily pretreated mCRPC were enrolled. At doses of 30 mg or higher, 25% achieved a ≥50% PSA reduction, and 16% achieved a ≥90% reduction. Median survival was 17.3 months versus 10.3 months at lower doses. However, immune activation brought risks: 75% of patients experienced side effects, and 14% suffered severe immune reactions, including two fatalities. The strongest responders were also those most prone to toxicity.
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• GSK5764227​
  GSK5764227 (HS-20093) is an ADC targeting B7-H3, a protein highly expressed in aggressive prostate tumors but rare in healthy tissues. Preclinical studies showed promising antitumor activity, and a global Phase I trial is now enrolling patients with advanced solid tumors, including mCRPC. Phase 1a focuses on safety, testing GSK5764227 alone and with standard therapies like cisplatin or pembrolizumab, while Phase 1b expands to specific cancer types to assess tumor responses and progression-free survival.
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• Q702​
  Q702 was tested on 51 patients with advanced solid tumors. While the study did not specifically highlight prostate cancer, its focus on solid tumors and its mechanism make it highly relevant for men battling metastatic castration-resistant prostate cancer (mCRPC). Q702 works by blocking three proteins—Axl, Mer, and CSF1R—that tumors use to grow, spread, and evade the immune system. In prostate cancer, Axl and Mer contribute to drug resistance (such as resistance to enzalutamide), while CSF1R helps tumors hide from immune attacks. By blocking these pathways, Q702 not only slows tumor growth but also helps the body’s immune system fight back. Of the patients evaluated, 12 achieved stable disease, with six maintaining it for over 16 weeks.

Preclinical Research

• Pimitespib​
  Pimitespib, an HSP90 inhibitorapproved in Japan for gastrointestinal cancers, may overcome resistance to androgen receptor pathway inhibitors (ARPIs)like enzalutamide and abiraterone in mCRPC. HSP90 stabilizes proteins that drive therapy resistance, including AR, AR-V7, GR, and AKT. In lab studies, pimitespib disrupted these proteins, enhanced ARPI effectiveness, and blocked nuclear signaling pathways fueling cancer growth. In animal models, pimitespib combined with enzalutamide showed strong tumor-shrinking effects without major toxicity.
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• Orally Delivered CRISPR Therapy​
  Scientists have developed an oral CRISPR-Cas9 delivery system that targets the TRAP1 gene, which drives chemotherapy resistance and immune suppression. Although studied in colorectal cancer models, the innovation could extend to prostate cancer. Encased in nanocomplexes and coated with trimethylamine oxide (TMAO), the therapy survives digestion and homes to tumors. In mouse models, combining the CRISPR therapy with 5-fluorouracil achieved a 93.3% tumor suppression rate and nearly doubled survival, while boosting immune-friendly cells and dismantling suppressive tumor environments. This approach could revolutionize treatments for otherwise resistant (“cold”) tumors.
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• 225Ac-Macropa-PEG4-YS5​
  This CD46-targeted therapy delivers the radioactive isotope 225Ac to prostate cancer cells. CD46 is overexpressed in both adenocarcinoma and neuroendocrine prostate cancers but remains scarce in healthy tissues, making it a promising target. In preclinical studies, 225Ac-Macropa-PEG4-YS5 eradicated small tumors (<1 mm), shrinking them and improving survival in animal models. However, larger tumors (>1 mm) showed uneven radiation distribution, highlighting the importance of early intervention. This approach could benefit patients with small, spreading tumors or PSMA-negative disease, including those with liver metastases.
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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