LAST WEEK TODAY!

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

Hi fellow warriors!
​First of all, thank you! The target has been reached. Thanks to your donations, I can renew our subscription to Kit.com and keep sending the newsletters!​
This week we have a great mix of clinical and preclinical research, including some studies of major significance! 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 AMPLITUDE Trial: Niraparib Combined with Abiraterone Acetate for HRR-Deficient mCSPC​
  The AMPLITUDE trial, a recently published randomized Phase 3 study in Nature Medicine, evaluated the benefit of adding the PARP inhibitor niraparib to standard abiraterone acetate and prednisone in men with metastatic castration-sensitive prostate cancer (mCSPC) harboring specific homologous recombination repair (HRR) gene mutations.
  Among 696 genomically profiled patients, deleterious alterations were identified in genes including BRCA1, BRCA2, BRIP1, PALB2, RAD54L, and CHEK2. The addition of niraparib significantly improved radiographic progression-free survival (rPFS): in patients with BRCA1/2 mutations, median rPFS was not reached in the combination arm versus 26.0 months in the control, reflecting a 48% reduction in risk of progression or death (HR 0.52). In the overall population, median rPFS was not reached with niraparib versus 29.5 months with control (HR 0.63). These findings support incorporating PARP inhibition early in mCSPC management for patients with HRR gene alterations.
  ​
  ​
• Phase 3: ASPIRE Trial — Early Docetaxel Addition to Apalutamide for mCSPC
  ​The ASPIRE trial is a large, ongoing Phase 3 multicenter study led by the Alliance for Clinical Trials in Oncology, enrolling 1,200 men with mCSPC. It investigates whether early intensification with docetaxel chemotherapy alongside hormone therapy and apalutamide improves overall survival. Patients are randomized to standard hormone therapy plus apalutamide or to the same regimen with six cycles of docetaxel.
  Key secondary endpoints include progression-free survival and quality of life. The trial also integrates genomic profiling to identify whether mutations in TP53, PTEN, or RB1 predict enhanced benefit from treatment intensification, marking a step toward personalized systemic therapy in mCSPC.
  ​
  ​
• Phase 2 LUNAR Trial: PSMA Radioligand Therapy Combined with SBRT for Oligorecurrent Prostate Cancer
  ​The Phase 2 LUNAR trial explored combining PSMA-targeted radioligand therapy with stereotactic body radiotherapy (SBRT) in 92 men with oligorecurrent prostate cancer. Participants received either SBRT alone or two injections of ¹⁷⁷Lu-PNT2002 followed by SBRT to visible lesions. The combination achieved a median progression-free survival (PFS) of 17.6 months, more than double that of SBRT alone (7.4 months), and delayed the need for hormone therapy (24.3 vs 14.1 months). The risk of relapse, hormone initiation, or death was reduced by 63%, without significant added toxicity beyond mild white blood cell reductions.
  ​
  ​
• Phase 2b: Cabazitaxel vs ARPIs in Poor-Prognosis mCRPC Post-Docetaxel
  ​This multicenter, open-label Phase 2b trial compared cabazitaxel chemotherapy with androgen receptor pathway inhibitors (ARPIs)—abiraterone plus prednisone or enzalutamide—in poor-prognosis metastatic castration-resistant prostate cancer (mCRPC) after docetaxel. The 12-week clinical benefit rate (CBR) showed no significant difference (overall 62.3%). Both rPFS and overall survival were comparable, though PSA50 responses favored ARPIs (47.2% vs 26.9%). Notably, prior ARPI exposure predicted poorer outcomes upon ARPI retreatment but not with cabazitaxel. Grade ≥3 adverse events occurred more frequently with cabazitaxel (65.4% vs 30.2%).
  ​
  ​
• Phase 1: ¹⁶¹Tb-PSMA Radioligand Therapy for ¹⁷⁷Lu-PSMA–Refractory mCRPC
  ​A multicenter Phase 1 study provided the first human data on terbium-161-labeled PSMA (¹⁶¹Tb-PSMA) for mCRPC progressing after ¹⁷⁷Lu-PSMA (Pluvicto). Terbium-161 emits both beta-minus particles and Auger electrons, the latter potentially improving micrometastatic control. Among seven heavily pre-treated patients, 57% achieved objective imaging responses and ≥50% PSA reduction, with an excellent safety profileandno Grade ≥3 toxicities reported. These promising results position ¹⁶¹Tb-PSMA as a potential next-generation radiopharmaceutical salvage therapy for advanced mCRPC.
  ​​
  ​
• Phase 1: VIR-5500 Dual-Masked T-Cell Engager for mCRPC
  VIR-5500 is a dual-masked T-cell engager targeting PSMA for mCRPC treatment, using PRO-XTEN masking technology to enable tumor-selective T-cell activation while minimizing off-target toxicity. The ongoing Phase 1 trial, now in Part 3, involves combination therapy with an androgen receptor signaling inhibitor (ARSI) in taxane-naïve patients, aiming to enroll 390 participants.
  Interim results show no dose-limiting toxicities and only mild cytokine release syndrome (CRS), validating the dual-mask mechanism. PSA declines were observed in all treated patients, with 58% achieving ≥50% reduction. VIR-5500 demonstrates potential as monotherapy or combination therapy, even in heavily pretreated populations.
  ​
  ​

Preclinical Research & Reviews

• Lipid Nanoparticle Vaccine for Cancer Immunoprevention​
  Preclinical research revealed a lipid nanoparticle vaccine that robustly prevents melanoma, pancreatic cancer, and triple-negative breast cancer in animal models. The vaccine co-delivers tumor-specific antigens and dual immune-stimulating adjuvants within one nanoparticle, activating both innate and adaptive immunity.
  Tumor rejection rates reached 88% in pancreatic cancer, and vaccinated, tumor-free mice resisted metastasis after systemic challenge. The platform shows strong promise for prostate cancer immunotherapy, capable of targeting PSMA, PAP, and PSA antigens to elicit potent T-cell responses. Beyond prevention, prior studies indicate therapeutic efficacy in eradicating established tumors, highlighting its potential in both preventive and therapeutic cancer vaccination.
  ​
  ​
• TexPSR Pathway: A Mechanism of T-Cell Exhaustion in Immunotherapy Failure
  ​A Nature study from The Ohio State University Comprehensive Cancer Center identified a key driver of T-cell exhaustion, termed the TexPSR (proteotoxic stress response) pathway. Excessive protein synthesis induces proteotoxic shock in T cells, leading to immune failure and resistance to immunotherapy across multiple cancers.
  Targeting TexPSR restored T-cell function and significantly improved immunotherapy responses in preclinical models, providing a new therapeutic avenue to overcome T-cell dysfunction in prostate cancer, a major barrier to current immunotherapies.
  ​
  ​
• GlyTR: “Velcro-Like” Immunotherapy Targeting Tumor Carbohydrate Antigens
  ​Researchers at UC Irvine, in a study published in Cell, developed a new immunotherapy platform called GlyTR, which uses a “velcro-like” binding mechanism to target tumor-associated carbohydrate antigens (TACAs) that are densely expressed on cancer cells.
  GlyTRs are bispecific proteins combining lectin domains (which bind sugars) with antibody fragments that engage T cells. This density-based binding enables high tumor selectivity while sparing normal tissue. Preclinical data showed potent T-cell–mediated killing across multiple cancers, including prostate cancer, even in immunosuppressive environments. GlyTR1 is advancing toward Phase 1 clinical testing within two years for metastatic solid tumors.
  ​

​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.

If you this newsletter was delivered to your SPAM folder, make sure to let your email system know that it is not spam.
​
​
Have a great weekend!

Max