LAST WEEK TODAY!

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

Hi fellow warriors! This week’s newsletter is more concise, spotlighting clinical trials over preclinical research. 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.
​For more details on everything I talk about here, you can always visit ProstateWarriors.com.​

Clinical Research

• Phase 1 Study: KTX-2001 for mCRPC
  The U.S. Food and Food and Drug Administration (FDA) has cleared the way for the first clinical trial of an NSD2 inhibitor in metastatic castration-resistant prostate cancer (mCRPC), approving the Investigational New Drug application for KTX-2001. This oral, selective therapy will be tested in a Phase 1 study known as STRIKE-001, which will enroll patients whose cancer has progressed despite at least one androgen receptor–targeted treatment. The trial will explore KTX-2001 both as a single agent and in combination with the androgen receptor blocker darolutamide, with enrollment expected to begin in the third quarter of 2025. NSD2 has emerged as a powerful driver of aggressive prostate cancer, being markedly elevated in advanced and treatment-resistant forms of the disease, including neuroendocrine variants, and contributing to an immune-suppressive tumor microenvironment. Preclinical models showed that inhibiting NSD2 disrupts cancer-promoting programs, sharply reducing tumor growth and preventing metastases.
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• Phase 1/2 Trial: INKmune in mCRPC
  A recent Phase 1/2 clinical trial, the CaRe PC trial, evaluating INKmune, an investigational immunotherapy for men with metastatic castration-resistant prostate cancer (mCRPC), has met its primary and secondary endpoints, demonstrating a favorable safety profile and signs of biological activity. INKmune is a pharmaceutical-grade, replication-incompetent human tumor cell line designed to prime resting natural killer (NK) cells and transform them into memory-like NK cells capable of effectively targeting tumor cells. The study enrolled up to 30 patients across multiple U.S. sites and found that INKmune was well tolerated across all dose levels, achieving its primary safety endpoint with no significant adverse events. Biomarker analyses revealed effective activation of NK cells in over half the treated patients, most notably in those with low baseline NK cell activation, which helped identify a target population that may benefit most. Although not primarily designed for efficacy, some participants showed reductions in tumor lesion size, with a few lesions disappearing altogether, suggesting potential direct antitumor effects. Encouraged by these results, the sponsoring company plans to advance INKmune into a randomized Phase 2b trial involving patients with less severe disease.
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• Phase 1b/2 Study: TYK-00540 Combined With Enzalutamide in mCRPC
  An open-label, multi-center Phase 1b/2 clinical trial is evaluating the safety and preliminary antitumor activity of TYK-00540 in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) who have previously failed novel endocrine therapies. TYK-00540 is a novel oral small-molecule inhibitor that simultaneously targets cyclin-dependent kinases 2, 4, and 6 (CDK2/4/6), key enzymes that regulate cell cycle progression and tumor cell proliferation. By blocking these kinases, TYK-00540 aims to overcome resistance mechanisms seen with existing CDK4/6 inhibitors and more effectively disrupt cancer cell growth. This dual targeting of cell cycle progression and androgen signaling pathways represents a rational strategy to address tumor growth driven by multiple mechanisms, potentially offering a new therapeutic option for advanced prostate cancer resistant to standard hormonal treatments.
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• Phase 1b/2 Clinical Trial: TY-302 and Abiraterone Acetate in mCRPC​
  A new Phase Ib/II study will evaluate the safety and efficacy of TY-302, a CDK4/6 inhibitor, combined with Abiraterone acetate in patients with metastatic castration-resistant prostate cancer (mCRPC) who have failed novel endocrine therapies like enzalutamide or apalutamide. TY-302 works by targeting cyclin-dependent kinases 4 and 6 to halt cancer cell proliferation, while Abiraterone inhibits androgen production. The combination seeks to address both cell cycle and androgen signaling pathways, potentially overcoming resistance in patients with limited treatment options. This study builds on Abiraterone’s established role and explores the emerging use of CDK4/6 inhibitors in prostate cancer, where such agents are less common compared to breast cancer.
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• Phase 2 Trial: Tarlatamab for Neuroendocrine Prostate Cancer (NEPC)
  A Phase 2 open-label study is investigating tarlatamab, an immunotherapy designed as a bispecific T-cell engager, in patients with neuroendocrine prostate cancer (NEPC), a particularly aggressive form of prostate cancer with limited treatment options. Tarlatamab targets delta-like ligand 3 (DLL3), a protein highly expressed on NEPC tumor cells but absent in most other prostate cancers, enabling it to recruit and activate T cells to selectively attack cancer cells expressing DLL3. The trial focuses on adults with metastatic de novo or treatment-emergent NEPC who have often undergone multiple prior treatments. While side effects like low-grade cytokine release syndrome are frequent, early results show they are generally manageable and reversible without requiring discontinuation of treatment. Among patients with DLL3-positive tumors, preliminary evidence indicates a higher objective response rate and improvements in progression-free survival.

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Preclinical Research

• New Bacterial Therapy Destroys Tumors in Immunocompromised Animal Models
  A team of researchers in Japan has developed a novel bacterial therapy, AUN, that can attack tumors without relying on the patient’s immune system, presenting a potential benefit for individuals whose immunity is weakened by chemotherapy, radiation, or other conditions. Unlike current immunotherapies, AUN combines two naturally occurring bacteria: “Proteus mirabilis” (A-gyo) and “palustris” (UN-gyo), which, when administered intravenously, preferentially accumulate in tumors. Once in the tumor, the bacteria cause intratumoral blood clotting, vascular collapse, platelet aggregation, and extensive tumor cell death, likely involving bacterial toxins and biofilm formation. In animal models of various cancers, including those lacking functional immune cells, repeated doses of AUN produced high rates of complete tumor regression without evidence of systemic toxicity or cytokine release syndrome. While these naturally occurring bacteria are not genetically modified and their activity can be halted with antibiotics, the use of live bacteria raises questions about possible infection risks, drug resistance, and long-term safety that require further study before the therapy can advance to human trials.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max