LAST WEEK TODAY!

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

Hello fellow warriors! Another encouraging week for prostate cancer research, with several promising developments worth watching. 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: Aglatimagene Besadenovec (CAN-2409) Induces Lasting Immune Remodeling in Localized Prostate Cancer
  ​The randomized, placebo-controlled phase 3 PrTK03 trial evaluated locally injected aglatimagene besadenovec (CAN-2409) combined with oral valacyclovir alongside radiotherapy in men with intermediate- to high-risk localized prostate cancer. Long-term biomarker analysis using AI-assisted digital pathology demonstrated that CAN-2409 significantly increased overall lymphocyte fractions and tumor-infiltrating immune cells for more than two years post-treatment. At a median follow-up of 58 months, CAN-2409 delivered a 41% reduction in the risk of disease recurrence or prostate cancer-specific death (HR 0.59) in intermediate-risk disease. Additionally, systemic blood profiling from the ongoing PrTK05 study indicated parallel expansion of active, multiplying CD8+ effector and memory T cells.​
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• Phase 3 Trial: Eight-Year PACE-A Results Support SBRT Over Surgery for Localized Prostate Cancer
  ​The randomized phase 3 PACE-A trial directly compared five-fraction stereotactic body radiotherapy (SBRT) (36.25 Gy in 1–2 weeks) against radical prostatectomy in 123 men with low- or intermediate-risk localized prostate cancer. At an eight-year median follow-up, SBRT achieved long-term cancer control comparable to surgery, with freedom-from-failure rates of 91.2% for SBRT versus 83.7% for prostatectomy. SBRT was superior in patient-reported quality of life, demonstrating significantly lower rates of urinary incontinence (8.3% vs. 48.3% daily pad usage at five years) and superior preservation of erectile function.
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• Phase 2/3 Trial: 68Ga-DOTA-RM2 GRPR-Targeted PET Imaging as a Novel Theranostic Platform
  ​The pivotal phase 2/3 SPARROW trial is evaluating 68Ga-DOTA-RM2, a PET tracer targeting the gastrin-releasing peptide receptor (GRPR), in approximately 400 patients with high-risk or suspected metastatic prostate cancer undergoing radical prostatectomy and lymph node dissection. By correlating imaging findings directly with surgical tissue pathology, the study aims to establish GRPR as a complementary biological target to PSMA for tumors with low or heterogeneous PSMA expression. Because the DOTA chelator can also bind therapeutic isotopes such as lutetium-177, RM2 provides a versatile theranostic platform capable of transitioning from diagnostic PET imaging to targeted radioligand therapy.
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• Phase 2 Trial: Single-Agent Carboplatin Demonstrates Activity in HRR-Altered mCRPC
  ​The single-arm phase 2 CIPHER trial investigated single-agent carboplatin administered every three weeks in 39 men with metastatic castration-resistant prostate cancer (mCRPC) harboring homologous recombination repair (HRR) gene alterations who had progressed on androgen-receptor pathway inhibitors. Carboplatin achieved a PSA50 response rate of 41% and a partial objective radiological response rate of 20%, with a median response duration of 6.2 months. Multivariable analysis showed that patients with germline HRR alterations were markedly more likely to respond than those with somatic-only mutations (OR 6.76).
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• Prospective Clinical Trial: ASTuTE Study Evaluates AI Biomarkers to Guide ADT Selection
  ​The prospective ASTuTE clinical trial is examining whether the ArteraAI Prostate Test,which analyzes digitized biopsy slides and clinical data, can guide androgen deprivation therapy (ADT) decisions in intermediate-risk prostate cancer. In an interim analysis of 200 patients, biomarker results changed the final shared treatment decision in 27.5% of cases, leading 70.3% of men who originally planned to receive short-term ADT to safely omit hormone suppression. Overall ADT utilization dropped from 37% prior to testing to 12.5% afterwards, demonstrating a significant reduction in unnecessary treatment, particularly within unfavorable intermediate-risk disease.

Preclinical Research & Reviews

• Targeting Metastasis: TTX-MC138 Shows Early Clinical Activity​
  A first-in-human Phase 1 trial tested TTX-MC138, an iron-oxide nanoparticle carrying an anti-miR-10b oligonucleotide, in 14 efficacy-evaluable patients with heavily pretreated advanced solid tumours. By blocking miR-10b, a microRNA linked to metastatic invasion and tumour-cell survival, the treatment achieved stable disease in 71.4% of patients; 35.7% remained progression-free at six months, and three patients at one year. No dose-limiting toxicities were reported.TTX-MC138 is not prostate cancer-specific, but the mechanism could still be relevant because miR-10b has been linked to metastatic behaviour in prostate cancer.
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• NADIR Clinical Model Validated to Predict Deep PSA Response in ARCHES Dataset
  ​A retrospective validation analysis evaluated the NADIR clinical model using data from 558 enzalutamide-treated patients in the phase 3 ARCHES trial to predict deep PSA suppression (PSA ≤0.2 ng/mL within six months) in metastatic hormone-sensitive prostate cancer. Utilizing baseline clinical variables such as PSA, hemoglobin, disease volume, and visceral metastases, the model demonstrated robust predictive accuracy with an AUC of 0.80. Patients in the highest predicted-response tier achieved a 92% deep PSA response rate compared to 37% in the lowest tier, with higher predicted probabilities also correlating with significantly longer overall survival.
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• ATM Alterations Predict Enhanced Sensitivity to Lu-177-PSMA Radioligand Therapy
  ​A retrospective genomic analysis of 205 mCRPC patients treated with 177Lu-PSMA-617 (Pluvicto) identified ATM gene alterations in 12.7% of cohorts, which served as an independent predictor of superior clinical outcomes across all endpoints. Patients with ATM alterations exhibited nearly triple the odds of achieving a PSA50 response (OR 2.91) alongside significantly prolonged progression-free survival (HR 0.40) and overall survival (HR 0.39) compared to ATM-wild-type patients. Conversely, BRCA2 alterations conferred no survival advantage, while CDK12 alterations predicted significantly worse survival (HR 2.58), demonstrating that individual HRR genes respond differently to radioligand therapy.
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• Dual-Target Radioligand INN02 Demonstrates Enhanced Tumor Uptake Against FAP and αvβ3
  ​Preclinical evaluation of INN02,a heterodimeric radioligand engineered to co-target fibroblast activation protein (FAP) and integrin αvβ3 in the tumor microenvironment, demonstrated marked superiority over single-target FAP agents. In animal models, 68Ga-INN02 achieved 11.65% injected dose per gram tumor uptake, while 177Lu-INN02 reached 21.96% uptake, significantly slowing tumor growth and extending median survival. Tissue analysis revealed that FAP was expressed in 58% of PSMA-negative castration-resistant tumors, while αvβ3 PET detected 78.4% of bone metastases, establishing proof-of-principle for dual-target theranostics in advanced disease.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max