LAST WEEK TODAY!

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

Hello fellow warriors! Research is accelerating, and we have more good news to share with you. 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: MAO-A Inhibition With ITR-251 to Overcome Prostate Cancer Resistance​
  A Phase 1 clinical trial is evaluating ITR-251, an experimental inhibitor of monoamine oxidase A (MAO-A), for patients with advanced solid tumours and metastatic castration-resistant prostate cancer (mCRPC). Although MAO-A is best known for breaking down neurotransmitters, laboratory research indicates it also supports biological processes that help malignant prostate cells survive despite androgen suppression. The first stage of the trial investigates ITR-251 as a monotherapy to evaluate safety, tolerability, and recommended dosing, while a subsequent stage will test ITR-251 alongside ongoing androgen deprivation therapy (ADT) and an androgen receptor pathway inhibitor (ARPI) in mCRPC.

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• Phase 1/2 Trial: Combining GI-102 With Pasritamig in Advanced Prostate Cancer​
  The JET-201 phase 1/2 clinical trialplans to enrol 107 patients with mCRPC to evaluate the combination of pasritamig (JNJ-78278343) and GI-102.Pasritamig is a bispecific antibody targeting KLK2 and CD3 that redirects T cells to prostate cancer cells, whereas GI-102 is an immune-stimulating fusion protein combining CD80 with modified interleukin-2 (IL-2) signaling to strengthen T-cell activity. In a prior phase 1 study of heavily pretreated mCRPC patients, pasritamig monotherapy demonstrated preliminary activity, achieving a PSA reduction of at least 50% in 42.4% of efficacy-evaluable patients and a median radiographic progression-free survival of 7.85 months.
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• Phase 2 Trial: Vaccine Plus PSMA×CD3 Immunotherapy in Biochemical Recurrence
  ​A randomized phase 2 trial is enrolling up to 84 patients with biochemical recurrence of prostate cancer following local curative treatment to evaluate a novel multi-arm immunotherapy strategy. Patients are randomized 1:1:1 to receive the prostate cancer multi-peptide vaccine VAC-XS15-PC01 alone, the PSMA×CD3 bispecific antibody CC-1 alone, or the two therapies in combination without concurrent anticancer treatment. CC-1 binds PSMA on cancer cells and CD3 on T cells to physically redirect immune attack, while VAC-XS15-PC01 contains peptides combined with the TLR1/2 agonist XS15to expand prostate cancer-specific T cells. The trial directly compares monotherapies against the combination to test whether vaccine priming enhances bispecific T-cell engagement in a low-tumour-burden setting, using PSA50 response as a key efficacy measure.
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• Phase 2 Trial: Tinengotinib With Darolutamide or Enzalutamide in Hormone-Resistant Prostate Cancer​
  A newly registered phase 2 clinical trial is investigating whether combining tinengotinib (TT-00420) with darolutamide or enzalutamide improves disease control in men with mCRPC. Tinengotinib is an oral multikinase inhibitor targeting FGFR, JAK, VEGFR, and Aurora kinases, acting on alternative molecular pathways that contribute to hormonal treatment resistance and neuroendocrine features.Preclinical studies demonstrated activity in enzalutamide-resistant models, while early clinical studies reported an objective response rate of 33.3% among 15 prostate cancer patients.
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• Phase 2 Trial: LUNAR Trial Follow-Up on Earlier PSMA Radioligand Therapy​
  Longer-term follow-up from the randomized phase 2 LUNAR trialdemonstrates that adding 177Lu-PNT2002 to stereotactic body radiotherapy (SBRT) delivers sustained clinical benefit in oligorecurrent hormone-sensitive prostate cancer. The study enrolled 92 men with 1–5 PSMA PET-positive metastases who were not on continuous ADT. At an extended median follow-up of 31.9 months, the combination arm maintained a 62% reduction in the risk of disease progression or starting hormonal therapy compared to SBRT alone. Furthermore, 33% of patients receiving the radioligand combination had no detectable disease at two years (vs. 12% with SBRT alone), and fewer patients experienced widespread progression (>5 new sites) or developed castration-resistant prostate cancer.
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• Phase 2 Trial: ZZ-FIRST Trial of Talazoparib Plus Enzalutamide in Metastatic Prostate Cancer​
  The randomized phase 2 ZZ-FIRST trial evaluated adding the PARP inhibitor talazoparib to enzalutamide and ADT in 54 men with high-volume metastatic hormone-sensitive prostate cancer (mHSPC) regardless of HRR mutation status. At 12 months, 73% of patients in the combination arm achieved a PSA below 0.2 ng/mL compared to 64.7% on enzalutamide alone, a difference that was not statistically significant. Median radiographic progression-free survival was 45.3 months with the combination versus 31.1 months with enzalutamide alone, but exploratory analyses showed no statistically significant rPFS or overall survival advantage alongside higher toxicity. Tumor biopsy analyses further revealed that androgen receptor suppression did not functionally impair homologous recombination repair (via RAD51/γH2AX markers), challenging the hypothesis of ARPI-induced “BRCAness” in HRR-proficient tumours.​
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Preclinical Research & Reviews

• Doxycycline Shows Activity Against Prostate Cancer Bone Metastasis​
  Preclinical research indicates that the antibiotic doxycycline and the related compound methacycline can reduce prostate cancer bone metastasis in laboratory models. Researchers identified acetylated KLF5 (Ac-KLF5) as a key driver of bone metastasis and osteoclast activation, demonstrating that doxycycline acts via an Ac-KLF5–PGK1 pathway to decrease tumour-cell invasion, reduce bone breakdown, and slow metastasis in mice. Because doxycycline is inexpensive, widely available, and has extensive human safety data, it offers an attractive drug repurposing candidate, though findings remain entirely preclinicalwithout evidence of clinical efficacy in human patients.
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• New PSMA Radiohybrid Combines PET Imaging With Alpha Therapy​
  A preclinical study published in the Journal of Nuclear Medicine evaluated rhPSMA-10.1, a radiohybrid compound designed to integrate PET diagnostic imaging with targeted alpha therapy. The platform pairs ¹⁸F/La-rhPSMA-10.1 for PET imaging with ²²⁵Ac-rhPSMA-10.1 for therapy, achieving 2.2-fold higher tumour accumulation after 1 hour and 3.5-fold higher accumulation after 24 hours compared to ²²⁵Ac-PSMA-I&T in mouse models. Both alpha-emitting treatments significantly suppressed tumour growth with median survival exceeding 50 days compared to 12 days in untreated controls, while matching diagnostic and therapeutic biodistributions support personalized radiation dosimetry.
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And…that’s all folks! For today at least!
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Have a great weekend!

Max