LAST WEEK TODAY!

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

Hello fellow warriors! Summer is approaching, but research never stops!
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 Trial: The PROTEUS Trial of Perioperative Apalutamide
  ​The PROTEUS phase 3 trialdemonstrated that adding perioperative apalutamide to androgen-deprivation therapy (ADT) significantly improves outcomes for men with high-risk localized or locally advanced prostate cancer undergoing radical prostatectomy. The trial met its co-primary endpoints, achieving a pathological complete response or minimal residual disease rate of 8.9% in the apalutamide group compared to only 1.0% in the placebo group. Furthermore, the five-year metastasis-free survival was 78.2% with apalutamide versus 73.5% with placebo, representing a 20% relative reduction in the risk of metastasis or death. Secondary endpoints, including event-free survival and time to first subsequent treatment, also consistently favored the addition of apalutamide.​​
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• Phase 2 Trial: GV20-0251 Combined with Anti-PD-1 Therapy
  ​This phase 2 study evaluates GV20-0251, an experimental antibody designed to block a new immune brake called IGSF8, in combination with anti-PD-1 drugs for patients with advanced solid tumors, including metastatic castration-resistant prostate cancer (mCRPC). Because prostate cancer typically shows limited responses to PD-1/PD-L1 monotherapy, this trial investigates whether blocking IGSF8 can restore innate immune signaling and enhance the efficacy of checkpoint therapy. Preclinical work suggests that IGSF8 blockade increases NK-cell killing, dendritic-cell antigen presentation, and T-cell infiltration.The trial is open-label and aims to enroll 227 adults, with specific groups requiring IGSF8 positivity for enrollment.
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• Phase 2 Trial: Zanzalintinib Following Pluvicto Treatment
  Zanzalintinib is currently being tested in a phase 2 trial for patients with chemo-naïve mCRPC who have progressed after receiving Pluvicto (177Lu-PSMA-617). The drug is a next-generation multi-target tyrosine kinase inhibitor that blocks VEGFR2, MET, and TAM kinases to target the “angiogenic rebound” and immunosuppressive microenvironment that often develop after radioligand therapy. This sequencing strategy is conceptually attractive because it attacks the resistance pathways that emerge following PSMA-directed treatment without immediately resorting to the toxicities associated with taxane chemotherapy. By inhibiting these escape routes, zanzalintinib aims to bend the resistance trajectory of the disease in patients who still maintain good performance status.
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• Phase 1 Trial: First-in-Human Study of CD46 ImmunoPET
  ​The first-in-human phase 1 study of the immunoPET tracer 89Zr-DFO-YS5 has shown that it is well tolerated and highly effective at mapping metastatic burden in mCRPC. CD46 is a cell-surface protein that remains highly expressed in aggressive, late-stage prostate cancer, even in variants that are PSMA-negative or neuroendocrine. In clinical testing with 30 men, this tracer detected approximately 45% more bone lesions than conventional bone scans and 136% more soft-tissue lesions than CT. This technology serves as a true theranostic tool, as the CD46 target can also be exploited therapeutically with antibody-drug conjugates like FOR46 (FG-3246), which has already shown encouraging activity in early trials.
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• Phase 1 Trial: GRPR-Targeted Theranostic DOTA-STR-17126
  ​An early phase 1, first-in-human imaging trial has commenced in Australia to evaluate DOTA-STR-17126, a theranostic agent targeting the gastrin-releasing peptide receptor (GRPR). GRPR is overexpressed in prostate cancer and is present in approximately 23.5% of mCRPC cases that are PSMA-negative or low, making it a vital target for patients who cannot benefit from PSMA-targeted therapies. Participants receive gallium-68 DOTA-STR-17126 for PET imaging to detect tumors, and those with positive uptake may receive a low dose of lutetium-177 for SPECT imaging and dosimetry.
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• Phase 1 Trial: ABBV-969 Dual-Target ADC in mCRPC​
  ​ABBV-969 is a dual-target antibody-drug conjugate (ADC) that targets both PSMA and STEAP1, and recent phase 1 data update has confirmed a median radiographic progression-free survival (rPFS) of approximately 15 months in heavily pretreated mCRPC patients. This signal far exceeds the historical 4- to 5-month rPFS seen with cabazitaxel in similar populations. By binding to either antigen, the bispecific ADC can reach a broader range of tumor cells, which helps address the tumor heterogeneity often seen in late-stage disease.

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Preclinical Research & Reviews

• A Promising Drug Pair for Treatment-Resistant Prostate Cancer
  ​A recent preclinical study has identified a potent strategy for treating advanced mCRPC by combining two existing drugs, eltanexor and zotatifin, to attack the disease from multiple angles. The research found that simultaneously blocking XPO1 (a nuclear export protein) and EIF4A1 (a factor in protein translation) interferes with both the movement of key molecules and the cell’s ability to manufacture survival proteins. This combination was shown to reduce AR and AR-V7 signalingand trigger cancer cell death in patient-derived organoids and xenograft models. Because both agents have known mechanisms and safety profiles, this repurposing-like approach could significantly shorten the timeline for moving into clinical testing.
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• IVMT-Rx-4: Targeting Prostate Cancer Spread to Bone
  ​IVMT-Rx-4 is a preclinical stage compound designed to block a protein called MDA-9/Syntenin, which plays a critical role in helping prostate cancer cells invade tissue and colonize the bone. By interfering with this pathway, the drug makes it harder for cancer to settle in the bone niche and reduces signaling molecules like PDGF-AA and CXCL5 that facilitate metastasis. Animal studies have been encouraging, showing that IVMT-Rx-4 reduces bone metastases. Furthermore, when combined with docetaxel, the compound improved survival more effectively than either treatment alone, suggesting its potential as a future partner for standard therapies.

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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