LAST WEEK TODAY!

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

Happy Easter to all you warriors! While waiting for the AACR 2026 meeting, another update with interesting clinical and preclinical studies. Have a fantastic Easter! 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 1b/2 Trial: PRINCE Trial of Lu-PSMA-617 and Pembrolizumab
  ​The final results of the PRINCE trial demonstrate that combining the radioligand therapy 177Lu-PSMA-617 (Pluvicto) with the immunotherapy pembrolizumab produces deep and durable responses in advanced mCRPC. The trial reported a 76% PSA50 response rate and a median overall survival of 20.8 months (49% at 24 months), which is notable for a population with low tumor mutational burden. Researchers believe the radioligand therapy may provide an immunogenic priming effect, enhancing the efficacy of the checkpoint inhibitor and paving the way for future Phase 3 combination trials.​
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• Phase 1 Trial: Xaluritamig (AMG 509) Monotherapy for mCRPC
  ​This study evaluates xaluritamig, a STEAP1 x CD3 bispecific T-cell engager, specifically as a monotherapy for patients with metastatic castration-resistant prostate cancer (mCRPC) who have already failed standard treatments like androgen receptor inhibitors and taxane chemotherapy. The drug works by recruiting T-cells to attack cells overexpressing the STEAP1 protein, creating an immune synapse for targeted tumor destruction. Early dose-exploration data showed that 59% of patients achieved a PSA50 response at higher dose levels, highlighting its potential in heavily pretreated populations where traditional options are no longer effective.​
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• Phase 1 Trial: IDE034 Dual-Target ADC for Advanced Malignancies
  IDE034 is a novel bispecific antibody-drug conjugate (ADC) that targets both B7-H3 and PTK7, two proteins frequently overexpressed in aggressive prostate cancers. B7-H3 is a particularly significant target because it acts as an immunosuppressive checkpoint and is expressed in over 93% of castration-resistant cases. By using bispecific engineering, IDE034 aims to improve selectivity and broaden the therapeutic window for its TOP1 inhibitor payload, potentially offering a more precise treatment for patients who have developed resistance to AR inhibitors.​
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• Phase 1/2 Trial: MRT-2359 GSPT1 Degrader in Combination Therapy
  ​The investigational drug MRT-2359 is a molecular-glue degrader that targets the GSPT1 protein, disrupting protein synthesis in MYC-addicted tumor cells. Recent interim data revealed a 100% PSA response rate in a small subgroup of mCRPC patients with AR mutations, suggesting that these mutations may serve as a critical biomarker for treatment success. Due to these encouraging results, the program is expanding to a Phase 2 trial in late 2026 to test MRT-2359 in combination with the next-generation AR inhibitor apalutamide.​
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• Phase 1 Trial: RAD 402 Radiolabeled Monoclonal Antibody
  ​Patient dosing has officially begun for RAD 402, an anti-KLK3 (PSA) monoclonal antibody radiolabeled with Terbium-161 (Tb-161). This therapy is unique because Tb-161 emits both beta particles, which provide longer-range cytotoxicity, and Auger electrons, which cause highly localized DNA damage. This dual-emission approach is designed to selectively destroy KLK3-expressing tumor cells while minimizing exposure to healthy bone marrow, offering a new radiopharmaceutical option for advanced prostate cancer.​
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Preclinical Research & Reviews

• HY809382: PRC2 Degrader for Hormone-Resistant Prostate Cancer
  HY809382 is an oral drug designed to dismantle the PRC2 complex by degrading its key component, EED, rather than just inhibiting its function. This approach is specifically targeted at prostate cancers that have become resistant to hormone therapies like enzalutamide, often due to PRC2-driven gene silencing. In preclinical models, the drug was able to overcome EZH2 mutations that typically render standard inhibitors ineffective and showed synergistic tumor suppression when combined with enzalutamide.​
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• MMAE-Based LIV1 ADC for Sustained Tumor Control
  ​Researchers have developed a high-affinity antibody, 48D6, which targets the zinc transporter LIV1 found on 72% of prostate tumors. This ADC uses an MMAE payload, a microtubule-targeting agent that proved significantly more effective in prostate cancer models than Topo I inhibitors. Preclinical results were particularly impressive, showing sustained tumor control for over 70 days even after treatment had ceased, suggesting that optimizing payloads specifically for prostate biology is vital for clinical success.​
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• QL535: CD2-Based PSMA T-Cell Engager
  QL535 is a trispecific molecule designed to address the issue of T-cell exhaustion in solid tumors by providing a second co-stimulatory signal through CD2. By simultaneously targeting PSMA on cancer cells and engaging CD3 and CD2 on T-cells, QL535 maintains its killing power longer than traditional designs under chronic stimulation. Additionally, it has demonstrated a favorable safety profile in primates with lower inflammatory cytokine release compared to other co-stimulatory approaches.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max