LAST WEEK TODAY!

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

Here I am with the second newsletter from the site. Last week, I had to travel for work, so I might have missed something! Let’s dive right in.

We also have a podcast if you prefer to listen to the newsletter, you can find it HERE.​

Clinical Research

• AMPLITUDE Phase 3 Trial (NCT04497844): This trial is evaluating the efficacy of Akeega (niraparib, a PARP inhibitor, combined with abiraterone acetate and prednisone) compared to abiraterone acetate and prednisone alone in patients with metastatic castration-sensitive prostate cancer (mCSPC) who have HRR gene mutations. The trial has enrolled 696 patients across 387 sites and is expected to conclude in November 2024. The primary endpoint is radiographic progression-free survival (rPFS).
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• The FDA has accepted a supplemental new drug application (sNDA) for darolutamide (Nubeqa®) in combination with androgen deprivation therapy (ADT) for the treatment of patients with metastatic hormone-sensitive prostate cancer (mHSPC). This sNDA is based on data from the Phase 3 ARANOTE trial.The ARANOTE trial showed that darolutamide plus ADT reduced the risk of radiographic progression or death by 46%�compared to placebo plus ADT. The trial also indicated a favorable safety profile for darolutamide, consistent with previous findings, and did not identify any new safety concerns. If this sNDA is approved, it would expand the indication for darolutamide in mHSPC to include use with and without chemotherapy.
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• CAN-2409 Phase 3 Trial (PrTK03, NCT01436968): This placebo-controlled trial is assessing the efficacy of the immunotherapy drug CAN-2409 (aglatimagene besadenovec) combined with radiation therapy in patients with intermediate-high risk localized prostate cancer. It has enrolled 711 patients in the US and Puerto Rico, with disease-free survival as the primary endpoint.
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• Mevrometostat Phase 3 Trial (MEVPRO-1, NCT06551324): This trial is investigating mevrometostat in men with metastatic castration-resistant prostate cancer (mCRPC) previously treated with abiraterone acetate. The trial aims to enroll 600 patients and has rPFS as the primary endpoint.

Preclinical Research

• CTT2274: CTT2274 is a prodrug that targets Prostate-Specific Membrane Antigen (PSMA) on prostate cancer cells. Preclinical studies in mice have shown tumor remission and increased survival. The first clinical trial is planned for 2026.�Hang in there brothers!
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• Nodularin-R and Abiraterone: This research identified five genes potentially contributing to abiraterone resistance, with high PPP1CA expression linked to poorer prognosis. Silencing PPP1CA increased sensitivity to abiraterone, while overexpression had the opposite effect. Nodularin-R was found to inhibit PPP1CA and enhance abiraterone’s effectiveness against resistant CRPC cells in vitro and in vivo.
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• Olaparib Resistance: This study found a link between the number of “reversion mutations” in a patient’s DNA and survival time on olaparib, a PARP inhibitor. This research also found that olaparib treatment could cause tumors to regain DNA repair ability, defeating the purpose of olaparib itself.
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• Immunotherapy Resistance: This research focuses on overcoming immunotherapy resistance in prostate cancer by blocking the IRE1 signaling pathway. Blocking IRE1 in mouse models enhanced the effectiveness of checkpoint inhibitors, leading to reduced tumor growth and an increase in cancer-killing immune cells. Clinical trials are needed to evaluate this approach in humans.
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• Targeting EZH2: Researchers found that EZH2 drives tumor growth in castration-resistant prostate cancer (CRPC) that has become resistant to standard treatments. Targeting EZH2 or the TGF-β pathway could potentially re-sensitize tumors to androgen receptor therapies or enhance immunotherapy effectiveness. Curiously, this preclinical data was published (or maybe I was just slow in finding it) two days after I have published the news about a phase 3 EZH2 inhibitor…so we will soon have some news!

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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