LAST WEEK TODAY!

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

Hi fellow warriors! Summer is approaching (ok, apologies to our friends from down under), but research doesn’t stop! Once again this week, we’ve got major updates on clinical trials—and just one preclinical study, but it’s been carefully selected just for 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

• Talazoparib + Enzalutamide: Transformative for mCRPC with HRR Mutations​
  The TALAPRO-2 trial confirmed that combining talazoparib with enzalutamide significantly improves outcomes in men with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair mutations. In 399 HRRm-positive patients, the combination boosted overall response rates (69.4% vs. 39.1%), more than doubled radiographic progression-free survival (30.7 vs. 12.3 months), and extended overall survival (45.1 vs. 30.8 months). The benefits were particularly strong in men with BRCA2, PALB2, CDK12, and ATM mutations. BRCA1 showed some benefit, but data were limited by small sample size.
  ​
• Luxdegalutamide Shows Promise in mHSPC, Including Resistant Mutants​
  Luxdegalutamide (JSB462/ARV-766), a next-generation AR degrader (PROTAC), is showing early signs of effectiveness in metastatic hormone-sensitive prostate cancer (mHSPC). Unlike traditional AR blockers, it degrades the androgen receptor, including resistant forms like T878, H875, and L702H. Phase 1/2 data in mCRPC already show a 43% PSA50 response in patients with AR mutations, and current trials are evaluating its potential when combined with abiraterone. Side effects have been manageable, and the drug’s ability to overcome resistance could offer new hope for patients earlier in their treatment journey.
  ​
• 177Lu-FAP-2286: A Targeted Radioligand with Potential in Bone Metastases​
  Early data on 177Lu-FAP-2286, a peptide-based radioligand therapy, show it is well tolerated and effectively delivers radiation to tumor sites especially in bone metastases, common in prostate cancer. By targeting FAP on cancer-associated fibroblasts, the therapy creates a “crossfire” effect that damages nearby cancer cells while sparing healthy tissue. Side effects have been mostly mild, and dosimetry indicates favorable radiation distribution.
  ​
• ORIC-944 + AR Inhibitors: Durable, Deep PSA Responses in mCRPC​
  ORIC-944, a potent PRC2 inhibitor, is emerging as a strong candidate in mCRPC treatment. Combined with apalutamide or darolutamide, the Phase 1b trial showed a 59% PSA50 response rate (47% confirmed) and a 24% confirmed PSA90 response rateacross all dose levels. Many patients experienced durable responses lasting a year or more. The therapy was well tolerated, with minimal severe side effects, reinforcing its potential as a long-term treatment option for patients resistant to prior AR therapies.
  ​
• 177Lu-PSMA-I&T Offers Viable Radioligand Option in Heavily Treated mCRPC​
  In a prospective registry study, 177Lu-PSMA-I&T delivered encouraging results in heavily pretreated mCRPC patients. Nearly half showed a PSA response (41% partial, 17% PSA90), with 26% maintaining that response at 12 weeks post-treatment. Median overall survival was 13 months, and progression-free survival reached 6.5 months on imaging. Side effects, including anemia and thrombopenia, were largely manageable. These outcomes closely mirror those of 177Lu-PSMA-617, positioning PSMA-I&T as a strong alternative, especially in settings where Pluvicto is unavailable.

Preclinical Research

• QED-203: First-in-Class Drug Targeting TRPV6 for Resistant Prostate Cancer​
  QED-203, a novel inhibitor of the TRPV6 calcium channel, shows remarkable preclinical promise in advanced prostate cancer, especially in cases resistant to current therapies. It disrupts key cancer pathways (NFAT, WNT), induces ER stress, and promotes apoptosis, even in enzalutamide-resistant models. Impressively, it outperformed both enzalutamide and darolutamide in cells with AR mutations and the ARV7 splice variant. With good tolerability in animal models and a unique, non-hormonal mechanism, QED-203 may offer a different and better approach.

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