LAST WEEK TODAY!

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

Hello fellow warriors! No rest for the weekend! Some new promising trials and preclinical research for us. 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 1 Trial: 177Lu-DTPA-SC16.56 in Neuroendocrine Prostate Cancer
  ​Memorial Sloan Kettering Cancer Center is currently conducting a Phase I trial evaluating 177Lu-DTPA-SC16.56, a novel radiolabeled antibody, in patients with progressive, chemotherapy-relapsed neuroendocrine prostate and lung cancers. DLL3 is the primary therapeutic target of this drug, as it is expressed in approximately 76.6% of neuroendocrine castration-resistant prostate cancer (CRPC-NE) samples but only 12.5% of adenocarcinomas, which is highly advantageous because PSMA is frequently suppressed as tumors transdifferentiate toward neuroendocrine features. The drug molecule combines a humanized antibody (SC16.56) that binds DLL3 with a DTPA chelator and a beta-emitting radioisotope, lutetium-177, to deliver highly localized radiation that causes DNA damage and cell apoptosis. Preclinical tests demonstrated strong efficacy with complete responses and cures in prostate xenografts with reversible toxicity.​
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• Phase 3 Trial: EMBOLD Prostate-302 and Risvutatug Rezetecan (Ris-Rez)
  ​The EMBOLD Prostate-302 Phase 3 clinical trial is preparing to enroll approximately 684 participants with metastatic castration-resistant prostate cancer (mCRPC) to evaluate risvutatug rezetecan (Ris-Rez/GSK5764227). The study compares this experimental therapy against standard or best supportive care, which may include prednisone or prednisolone combined with enzalutamide or abiraterone. Risvutatug rezetecan is an antibody–drug conjugate (ADC) directed against B7-H3 (CD276), an attractive target that is broadly retained in 97% of castration-sensitive and 93% of castration-resistant biopsies during disease progression. In the prior Phase 2 ARTEMIS-003 trial, the therapy showed encouraging antitumor activity with confirmed objective response rates of 38.9% in taxane-pretreated patients and 50.0% in taxane-naive patients.​
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• Phase 3 Trial: Lutetium-177-NYM032 Radioligand Therapy
  ​A new pivotal Phase 3 clinical trial is evaluating the therapeutic lutetium-177 version of NYM032, a PSMA-targeted radioligand that can also be labeled with gallium-68 for matched PET diagnostic imaging. Following the VISION trial blueprint, this study will randomize 600 patients with heavily pretreated mCRPC in a 2:1 ratio to the radioligand plus best supportive care versus best supportive care alone. In an earlier Phase 1/2 trial, NYM032 showed a manageable safety profile and encouraging antitumor activity at very small doses compared to Pluvicto.
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Preclinical Research & Reviews

• PEACE-3 Post-Hoc Analysis of Radium-223 and Enzalutamide
  ​An exploratory post hoc analysis of the international, randomized phase 3 PEACE-3 trial evaluated blood-based biomarkers in patients with bone-metastatic mCRPC receiving radium-223 combined with enzalutamide. The combination therapy concentrated calcium-mimicking, alpha-emitting radium-223 in bone metastases while enzalutamide blocked systemic androgen receptor signaling. Within six months of treatment, confirmed 30% alkaline phosphatase declines (ALP-30) occurred in 56.5% of combination patients versus 50.8% on enzalutamide alone, with the combination cutting the median time to reach an ALP-30 response to 2.4 months compared to 3.7 months. For tumor burden, confirmed 90% PSA declines (PSA-90) at six months were achieved by 50.5% on the combination versus 34.1% on monotherapy, with a dramatically faster median time to response of 5.6 months compared to 22.1 months.​
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• Feasibility of ADT and ARPI De-escalation Therapy
  ​A retrospective cohort study published in Clinical Genitourinary Cancer evaluated 69 men with metastatic prostate cancer (mHSPC or mCRPC) to determine if patients achieving a deep response can safely pause standard continuous androgen deprivation therapy (ADT) and androgen receptor pathway inhibitors (ARPI). The study reported a highly encouraging median treatment-free survival (TFS) of 35 months after stopping therapy, with 2-year and 5-year TFS rates of 56.2% and 33.8%, respectively. Initial hormone sensitivity (mHSPC) was the only independent predictor of a durable treatment break; more than half of the mHSPC patients remained treatment-free at the last follow-up. Furthermore, of the patients who eventually progressed, 96.3% successfully responded to a rechallenge of the same ADT and ARPI regimen, showing no evident loss of treatment sensitivity.​
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• TIGRa: A Compact Gene-Activation Switch Beyond CRISPR
  ​Stanford Medicine scientists have engineered a compact gene-activation tool named TIGRa that can switch on protective, therapeutic genes directly inside living cells. While traditional CRISPR gene-activation tools hold enormous promise, they are large and bulky, barely fitting inside the tiny viral vector delivery vehicles required to transport DNA instructions into human cells. To bypass this limitation, researchers engineered TIGRa using a compact natural microbial system discovered in 2025 (TIGR-Tas). TIGRa is less than half the size of comparable CRISPR tools, allowing it and instructions to activate multiple genes to fit comfortably within a single viral vector. In laboratory tests, TIGRa successfully turned on up to 12 different genes at the same time.​
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And…that’s all folks! For today at least!
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Have a great weekend!

Max