LAST WEEK TODAY!

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

Hi fellow warriors! I’m back again with some new research. Not even dinners with friends can stop me from publishing! 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: ProstACT Global for TLX591 Dosed the First Patient​
  ProstACT Global is a randomized Phase 3 study evaluating the PSMA-targeted radiopharmaceutical TLX591 (lutetium‑177 rosopatamab tetraxetan) in metastatic castration-resistant prostate cancer (mCRPC). Unlike small-molecule ligands, TLX591 is a lutetium-177-labeled humanized monoclonal antibody against PSMA that is internalized by tumor cells, delivering sustained beta-emitting radiation to metastases.
  A key differentiator is that the antibody’s large size leads to minimal uptake in the salivary and lacrimal glands, which is expected to substantially reduce common toxicities like dry mouth and dry eye associated with small-molecule PSMA therapies. And since TLX591 is predominantly cleared via the liver, kidney toxicity should also be improved.​
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• Phase 2 Trial: CONVERT-HB1 Study Design
  The CONVERT-HB1 trial is a Phase 2 study addressing the long-standing question of whether aggressively treating the primary prostate tumor adds meaningful benefit for patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) who are already receiving modern, intensified systemic therapy. This study specifically focuses on the high-volume population, a group historically deemed least likely to benefit from local control, and utilizes contemporary systemic treatmentslike ADT plus second-generation AR pathway inhibitors, potentially combined with docetaxel or PARP inhibitors. Crucially, the trial uses PSMA PET/CT not merely for staging but as a biomarker of “conversion success,” selecting high-volume patients whose metastatic lesions become metabolically silent after induction systemic therapy, effectively leveraging a functional, PSMA-based definition of deep response.​
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• Phase 1/2 Trial: GSK5764227 Antibody-Drug Conjugate
  GSK5764227 is a promising antibody-drug conjugate (ADC) designed to treat metastatic castration-resistant prostate cancer (mCRPC) by targeting B7-H3, a protein frequently overexpressed on prostate cancer cells. The ADC delivers a topoisomerase I inhibitor payload directly to the tumors, minimizing harm to healthy tissues. Early data from solid tumor studies showed the drug’s monotherapy potential, yielding objective response rates of approximately 60% in heavily pretreated patients across indications. The newest development is a phase 1b/2 sequential, non-randomized trial enrolling about 72 patients with histologically confirmed mCRPC to test GSK5764227 alongside enzalutamide.​
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• Phase 1/2 Trial: MHB048C PSMA-Targeted Therapy
  MHB048C is an investigational antibody–drug conjugate (ADC) designed to target prostate-specific membrane antigen (PSMA) on tumor cells, delivering a DNA topoisomerase I–inhibiting cytotoxic payload. This precision strategy aims to exploit the high and relatively restricted expression of PSMA in advanced prostate cancer, using PSMA as a validated target alongside topoisomerase I inhibition, a potent mechanism for inducing DNA damage,. By tethering the inhibitor to a PSMA-binding antibody, the goal is to internalize the conjugate and release the payload intracellularly, achieving higher effective intratumoral drug concentrations while mitigating the systemic exposure that often limits free topoisomerase inhibitors.​

Preclinical Research & Reviews

• Logic-gated DARPins for Solid Tumor Immunotherapy
  Logic-gated DARPins represent a significant preclinical advancement in immune therapy, promising enhanced safety and effectiveness for hard-to-treat solid tumors. This technology uses a “switch” design employing small, stable DARPin proteins that only activate T cells when two specific markers (like mesothelin and EpCAM in current research) are found together on cancer cells, essentially functioning as an “AND logic gate”,. This dual-signal activation prevents dangerous overactivation in healthy tissue, thus minimizing the risk of widespread cytokine storms associated with older T-cell engagers,. Furthermore, the small size of the DARPins allows for cheaper, faster production using bacterial systems and facilitates deeper tumor penetration. Although initial research focuses on ovarian cancer, DARPins are designed as independent modules that can potentially be customized to target antigens relevant to other cancer types, including prostate cancer.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max