LAST WEEK TODAY!

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

Hi fellow warriors! It looks like I’ll have to start updating the clinical trials table again. I thought I could rest for a while, but apparently science waits for no one! And even this week, there are quite a few surprises. 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 2 Trial: BRCAAway Survival Update
  The BRCAAway trial investigated the effectiveness of abiraterone and olaparib, administered either as single agents or in combination, for patients with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations (HRRm). Latest overall survival results indicate that the combination of abiraterone and olaparib achieved a median overall survival of 68 months, a significant increase compared to 28 months for abiraterone alone and 37 months for olaparib alone. These findings confirm that the combination therapy provides a median survival exceeding five years following the onset of castration resistance in mCRPC patients with BRCA1/2 or ATM mutations.​
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• Phase 1 Trial: MRT-2359 plus Enzalutamide
  The Phase 1 trial for MRT-2359 evaluated a daily pill designed to destroy proteins that drive cancer, such as the androgen receptor (AR), MYC, and Cyclin D1. Results from 18 heavily pre-treated patients showed that the drug, when combined with enzalutamide, was particularly effective in those with AR ligand-binding domain mutations. In these specific cases, all patients saw their PSA levels drop by at least 50%, and two patients experienced significant tumor shrinkage of over 60%.​
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• Phase 1b/2 Trial: Igermetostat and Enzalutamide
  The Phase 1b/2 study of Igermetostat (XNW5004), a selective EZH2 inhibitor, explored its use in combination with enzalutamide for patients who had previously failed novel hormone therapies like abiraterone. In a group of 53 post-abiraterone patients, the median radiographic progression-free survival (rPFS) was not yet reached at a 13.2-month follow-up, and the 12-month rPFS rate was 59.8%. Patients receiving the highest tested dose of 1200 mg twice daily showed an even higher 12-month rPFS rate of 70.8%.​
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• Phase 1 Trial: PAnTHa Study of PSMA-Trillium
  Initial data from the global PAnTHa trial focused on 225Ac-PSMA-Trillium, an experimental alpha radiation therapy that targets PSMA-expressing prostate cancer cells. The therapy was found to have a favorable safety profile with mostly mild side effects like dry mouth and fatigue, avoiding the severe toxicities seen in older actinium-based treatments. Among those receiving the recommended dose, 83% achieved a PSA50 response, and 46% of patients with measurable disease showed notable tumor shrinkage.​
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• Phase 2 Trial: SECuRE Update on Complete Responders
  An update from the SECuRE trial revealed that a fifth patient has achieved undetectable disease status through the use of 67Cu-SAR-bisPSMA. This 76-year-old patient with mCRPC saw his PSA levels become undetectable only seven weeks after his first treatment cycle, with imaging later confirming a complete lack of PSMA-avid disease. The trial is currently expanding its Phase II cohort to further evaluate the durability of these responses and optimal dosing strategies.​
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• Phase 1 Trial: VIR-5500 Dose-Escalation Results
  The Phase 1 trial for VIR-5500 demonstrated that this bispecific T-cell engager is a promising candidate for heavily pre-treated mCRPC patients. The drug uses masking technology to ensure it only becomes active within the tumor microenvironment, which resulted in a favorable safety profile with minimal cytokine release syndrome. Efficacy was high in the top dosing groups, with 82% of patients reaching a PSA50 response and 53% reaching a PSA90 response.​
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• Phase 1/2 Trial: UPLIFT Study on Boosting PSMA
  The UPLIFT trial is testing whether the CDK4/6 inhibitor abemaciclib can be used to increase PSMA expression on tumors, thereby enhancing the effectiveness of 177Lu-PSMA-617 radioligand therapy. By administering a 14-day “lead-in” of abemaciclib before the radiation dose, researchers hope to make tumors more receptive to the treatment without causing the severe side effects of long-term CDK4/6 blockade. Phase 1 data confirmed the safety of this pulse-dosing strategy in a group of battle-hardened mCRPC patients.​
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• pre|CISION Platform and AVA6103 Development
  The pre|CISION platform is designed to deliver potent chemotherapy payloads directly to tumors by exploiting the enzyme fibroblast activation protein (FAP) found in the tumor microenvironment. Preclinical data for AVA6103, an exatecan-based conjugate, showed it achieved significantly higher tumor selectivity and peak payload concentrations than existing antibody-drug conjugates. Following FDA clearance in early 2026, a Phase 1 clinical trial for this targeted therapy is expected to begin shortly.
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Preclinical Research & Reviews

• CT Muscle Measure as a Prognostic Tool
  Research derived from the STAMPEDE trial indicates that the skeletal muscle index (SMI), calculated from regular CT scans, is a reliable marker for predicting treatment response in newly diagnosed hormone-sensitive prostate cancer. Higher SMI levels were linked to a 15% reduction in the risk of death for every 10-unit increase in patients with metastatic disease. The study found that men within a specific SMI range (41 to 63) gained the most benefit from adding abiraterone to their treatment, while those with very high or very low muscle levels saw no additional survival advantage.​
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• Evolutionary Oncology and Immune Synergy
  Preclinical research has validated a new approach called “evolutionary oncology,” which suggests that radiation-resistant prostate cancer cells develop a unique vulnerability to natural killer (NK) immune cells. This “evolutionary double-bind” occurs because the proteins cancer cells use to resist radiation also act as targets that NK cells can recognize and attack. This discovery proposes a sequenced treatment strategy: first using radiation to drive the evolution of resistant cells, and then using NK-cell immunotherapy to eliminate them.​
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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