LAST WEEK TODAY!

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

Hi fellow warriors! I hope you’re doing well! Sending you some positive research vibes

Today, we have promising updates and innovative approaches tackling our disease from multiple angles. 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

• SECuRE Trial Shows Promising Results for 67Cu-SAR-bisPSMA in mCRPC
  The SECuRE trial, evaluating the novel radiopharmaceutical therapy 67Cu-SAR-bisPSMA for metastatic castration-resistant prostate cancer (mCRPC), has reported significant advancements. Notably, 92% of pre-chemotherapy participants experienced a greater than 35% reduction in prostate-specific antigen (PSA) levels after just one dose. Three participants in a multiple administration cohort achieved PSA reductions of 80% or more, with one achieving a complete response after two doses. The trial is now progressing to the Cohort Expansion Phase (Phase II) to further validate efficacy and safety, with a focus on pre-chemotherapy patients and an arm combining 67Cu-SAR-bisPSMA with enzalutamide. Earlier intervention with this therapy before chemotherapy could lead to better outcomes.
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• Phase III Trial Underway for 225-Ac-PSMA-617 and ARPI Combination in mCRPC​
  A new Phase III clinical trial is evaluating the combination of 225Ac-PSMA-617 and androgen receptor pathway inhibitors (ARPI) for PSMA-positive mCRPC. The study aims to determine if this combination improves radiographic progression-free survival (rPFS) compared to standard-of-care treatments in patients who have received an ARPI but not taxane-based chemotherapy in the mCRPC setting or prior PSMA-targeting radioligand therapy. Previous Phase I and II studies showed promising efficacy for 225-Ac-PSMA-617, including significant PSA declines in chemotherapy-naïve patients.
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• FG-3246 Advances to Phase 2 Trial for mCRPC
  ​FG-3246 (FOR46), a novel antibody-drug conjugate targeting CD46, is moving into a Phase 2 clinical trial for mCRPC. This trial will enroll approximately 75 patients who have received one second-generation ARSI but no prior taxane therapy in the castration-resistant setting. It will assess key efficacy measures such as PSA decline, objective response rate, radiographic progression-free survival, and overall survival. This follows encouraging Phase 1b results where FG-3246 combined with enzalutamide demonstrated a median radiographic progression-free survival of 10.2 months in biomarker-unselected patients who had progressed after at least one ARSI.
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• Phase I/II Trial Begins for Hypoxia-Reversing Agent IMGS-101 with Checkpoint Inhibitors​
  A Phase I/II clinical trial has been initiated to evaluate the hypoxia-modifying agent IMGS-101 (evofosfamide) in combination with checkpoint inhibitors for advanced solid cancers, including mCRPC. The trial aims to counteract hypoxia, a condition that can hinder T-cell infiltration and reduce the effectiveness of immunotherapy. By reversing hypoxia, IMGS-101 may enhance the efficacy of checkpoint inhibitors by improving T-cell access to tumors.
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• First-in-Human Trial for Macrophage-Drug Conjugate MDC-735 Expected in 2025​
  While still in preclinical stages, the first-in-human trial of MDC-735, a macrophage-drug conjugate, is set to launch in 2025 to evaluate its safety and efficacy in patients with solid tumors. This novel approach uses macrophages to deliver anticancer drugs directly to tumors, offering a potentially more targeted therapy with reduced systemic toxicity. Furthermore, MDCs may also modulate the tumor microenvironment and activate the immune systemÂfor a more durable anti-cancer response.
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Preclinical Research

• Androgen Receptor Inhibition May Enhance Immune Response in Prostate Cancer
  ​A preclinical study published in Cancer Discovery suggests that standard prostate cancer treatments like androgen deprivation therapy (ADT) and androgen receptor signaling inhibitors (ARSi) may have an unexpected benefit: making tumors more visible to the immune system. Researchers found that inhibiting the androgen receptor (AR) increases the presence of Major Histocompatibility Complex Class I (MHC-I) molecules on cancer cells. These molecules act as “flags” that allow immune cells, particularly T cells, to recognize and attack cancer cells. By increasing antigen presentation through MHC-I, AR inhibition could potentially transform immunologically “cold” prostate tumors into “hot” ones, making immunotherapy more effective. This suggests that current treatments might be priming cancer cells for an improved immune response, potentially leading to combination therapies integrating hormonal and immune-based approaches.
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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