LAST WEEK TODAY!

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

Hello fellow warriors! New findings from the ESMO 2026 meeting are starting to come in, and there’s plenty to talk about. So grab yourself something to drink, get comfortable, and enjoy! 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 Trial: Eight-Year Overall Survival Benefits in PEACE-1​
  After a median follow-up of 7.7 years, results from the Phase 3 PEACE-1 trial confirm a lasting survival advantage from adding abiraterone and prednisone to standard care in men with metastatic hormone-sensitive prostate cancer (mHSPC). Across the full trial population, adding abiraterone reduced the hazard of death by 25%. Among patients treated with ADT and docetaxel chemotherapy, abiraterone reduced death hazard by 32%, raising median overall survival from 4.4 to 6.2 years and eight-year survival from 27.1% to 40.3%. In patients with high-volume metastatic disease, eight-year survival nearly doubled from 20% to 38%.​
  ​
• Phase 3 Trial: DASL-HiCaP Metastasis-Free Survival Outcomes​
  The randomized Phase 3 DASL-HiCaP trial evaluated the addition of darolutamide to androgen deprivation therapy (ADT) and radiotherapy in 1,106 patients with high-risk localized or locally advanced prostate cancer. At a median follow-up of 3.8 years, darolutamide reduced the risk of metastasis or death by 58% (HR 0.42) compared to placebo. Four-year metastasis-free survival reached 95% with darolutamide versus 88% with placebo, while four-year PSA progression-free survival improved to 91% versus 83%.​
  ​
• Phase 3 Trial: PROTEUS Substudy Perioperative Apalutamide Benefits​
  A randomized substudy of the Phase 3 PROTEUS trial investigated perioperative apalutamide plus ADT before and after radical prostatectomy versus surgery alone in 408 patients with high-risk localized or locally advanced prostate cancer. At a median follow-up of 37.8 months, three-year event-free survival (EFS) was 63.0% in the treatment arm compared to 41.4% with surgery alone, representing a 62% reduction in the risk of progression or death (HR 0.38). Treatment also reduced the risk of metastasis or death by 51% (HR 0.49).​
  ​
• Phase 3 Trial: TALAPRO-3 Biomarker Findings Across HRR Gene Alterations​
  An exploratory biomarker analysis from the Phase 3 TALAPRO-3 trial evaluated talazoparib combined with enzalutamide across specific homologous recombination repair (HRR) gene subgroups in metastatic castration-sensitive prostate cancer (mCSPC). The combination reduced the overall risk of PSA progression by 49%. Subgroup analyses demonstrated PSA progression risk reductions across several genes BRCA2 (HR 0.45), CDK12 (HR 0.42), CHEK2 (HR 0.49), ATM (HR 0.61), and ATR (HR 0.25), though only the BRCA2 and CDK12 subgroups reached nominal statistical significance. Achieving deep PSA suppression (<0.2 ng/mL) at six months was associated with a 63% lower risk of radiographic progression or death.​
  ​
• Phase 2 Trial: ExBAT Analysis Linking AR Amplification to Poorer Outcomes​
  Biomarker results from the Phase 2 ExBAT trial, which tested alternating bipolar androgen therapy (supraphysiological testosterone) and darolutamide in post-abiraterone mCRPC, identified circulating tumor DNA (ctDNA) markers of resistance. Patients harboring androgen receptor (AR) alterations (30.4% of patients) experienced significantly shorter overall survival compared to those without alterations (median 12.3 months vs. median not reached). AR amplification was the primary driver of this difference, with a 12-month overall survival rate of 50% in patients with AR amplification versus 88.9% in those without.​
  ​
• Phase 2 Trial: DLL3 PET Imaging for Neuroendocrine Prostate Cancer​
  A prospective Phase 2 study evaluated ²⁸⁹Zr-DFO-SC16.56, an experimental PET tracer targeting DLL3, in 23 patients with confirmed or suspected neuroendocrine prostate cancer (NEPC).The tracer successfully identified positive lesions in 74% of patients. Intra-patient tumor heterogeneity was prominent: among patients with positive scans, 65% presented with both DLL3-positive and DLL3-negative metastases, underscoring the complex biology of NEPC.​
  ​
• Phase 2 Trial: CONVERGE-01 Evaluation of CONV01-α Alpha Radioligand​
  Part 2 of the Phase 2 CONVERGE-01 trial assessed CONV01-α (²²⁵Ac-rosopatamab tetraxetan), a PSMA-targeted antibody alpha therapy, in 19 mCRPC patients without prior Lu-PSMA or taxane chemotherapy for castration-resistant disease. Among 12 evaluable patients, 83% achieved a PSA reduction of at least 50% (PSA50)and 25% achieved a PSA90 response. Main safety concerns centered on hematological toxicity (Grade 3–4 lymphopenia in 45%; thrombocytopenia/neutropenia in 26%), while organ dosimetry confirmed no detectable activity in salivary glands.​
  ​
• Phase 1/2 Trial: Bavdegalutamide (ARV-110) PROTAC Activity by AR Mutation​
  Updated Phase 1/2 trial findings evaluated bavdegalutamide (ARV-110), an oral PROTAC androgen receptor degrader, in 239 heavily pretreated mCRPC patients. In a subgroup of 20 patients with AR T878 and/or H875 mutations, 60% achieved a PSA50 response and median radiographic progression-free survival (rPFS) reached 11.1 months. Conversely, PSA50 response rates were only 4.3% in patients with wild-type AR or other alterations and 3.1% in those with AR L702H mutations or AR-V7 expression.​
  ​
• Phase 1/2 Trial: EIK1003 Selective PARP1 Inhibitor Combination​
  The Phase 1/2 EIK1003-001 trial evaluated EIK1003 (a selective PARP1 inhibitordesigned to spare PARP2) in combination with abiraterone and prednisone in 34 patients with HRR-mutated prostate cancer (29 mCRPC, 5 mCSPC). Radiological partial responses occurred in 26.7% of evaluable patients, yielding an overall disease control rate of 93.3%. Grade 3 or higher anemia occurred in 11.8% of patients, supporting potential hematological safety advantages over non-selective PARP1/2 inhibitors.​
  ​
• Phase 1/2 Trial: Gedatolisib Plus Darolutamide Combination in mCRPC​
  Updated results from the Phase 1/2 CELC-G-201 trial evaluated gedatolisib (a PI3K–AKT–mTOR inhibitor) combined with darolutamide in 45 mCRPC patients previously treated with AR pathway inhibitors. Confirmed PSA50 responses occurred in 26.7% of patients overall and rose to 40.9% among those with prior abiraterone exposure. Median progression-free survival reached 9.1 months overall and 15.7 months in the prior-abiraterone cohort.​
  ​
• Phase 1 Trial: TheraPb Follow-Up Data for ²¹²Pb-ADVC001 Alpha Therapy​
  Longer-term Phase 1 results from the TheraPb trial evaluated ²¹²Pb-ADVC001, a PSMA-targeted lead-212 alpha radioligand, in 22 pretreated mCRPC patients. At a median follow-up of 14.1 months, median radiographic progression-free survival reached 11.2 months at the selected Phase 2 dose. Confirmed response rates included an 80% PSA50 response rate and a 100% objective response rate among patients with measurable disease.​
  ​
• Phase 1 Trial: ProTACT First-in-Human Study of ²²⁵Ac-FL-020​
  Results from the Phase 1 ProTACT trial evaluated ²²⁵Ac-FL-020, an investigational PSMA-targeted alpha radioligand, in 27 heavily pretreated mCRPC patients. Overall, 40.9% of evaluable patients achieved a PSA50 response, increasing to 83.3% (5/6) at the 6 MBq dose cohort. Dry mouth was limited to Grade 1–2 severity, and no dose-limiting toxicities were observed.​
  ​
• Phase 1 Trial: SHR-4394 PSMA-Targeted Antibody-Drug Conjugate​
  First-in-human Phase 1 trial data for SHR-4394, a PSMA-targeted ADC delivering a cytotoxic chemotherapy payload, were reported in 53 mCRPC patients. Among 42 evaluable patients with high PSMA expression (SUVmax ≥20), 40.5% achieved a PSA50 response and 35.3% achieved confirmed objective tumor responses. Grade 3 or higher treatment-related hematological toxicities occurred in 45.3% of patients, primarily neutropenia (34.0%) and anemia (15.1%).​
  ​
• Phase 1 Trial: SYNC-T Personalised Immunotherapy Survival Updates​
  Extended follow-up from the Phase 1 trial of SYNC-T (SV-102, a multi-agent intratumoral immunotherapy following partial tumor cryolysis) was reported in 15 metastatic prostate cancer patients. At a median follow-up of 29.6 months, two-year overall survival reached 80% (12/15 alive). Median overall survival was 27.9 months in mCRPC patients, while 100% of mHSPC patients were alive at two years.​
  ​
• Phase 1 Trial: First-in-Human Astatine-211 PSMA-5 Alpha Radioligand​
  A first-in-human Phase 1 trial evaluated ²¹¹At-PSMA-5, a short half-life (7.2-hour) astatine-211 alpha radioligand, in 15 mCRPC patients. In patients receiving dose levels of 2.0 MBq/kg or higher, 83% achieved a PSA50 response and 67% achieved a PSA80 response. Partial PET imaging responses were observed in 44% of evaluable patients, with no dose-limiting toxicities reported.​
  ​
• Phase 1 Trial: ABBV-969 Bispecific Dual PSMA/STEAP1 ADC​
  Molecular biomarker updates from the Phase 1 study of ABBV-969, a dual-targeting ADC directed against PSMA and STEAP1, were evaluated in 49 heavily pretreated mCRPC patients. By the start of the third treatment cycle, 90% of evaluable patients achieved a ≥50% reduction in ctDNA, and 57% achieved a ≥95% ctDNA reduction. Complete circulating tumor cell (CTC) clearance occurred in 47% of patients.​
  ​
• Phase 1 Trial: JNJ-6143 Oral RIPTAC Targeted Therapy​
  Updated Phase 1 study findings for JNJ-6143 (HLD-0915), an oral RIPTAC that forms an abnormal AR-BRD4 protein complex, were reported in 52 pretreated mCRPC patients. At the preliminary optimal dose of 50 mg daily (n=17), confirmed PSA50 and PSA90 response rates were 77% and 48%, respectively, with objective partial responses in 4 of 7 patients with measurable disease. Responses occurred across various genomic profiles, including patients with PTEN loss.​​
  ​
• Phase 1 Trial: ²²⁵Ac-LNC1011 Prolonged-Circulation Alpha Radioligand​
  Updated Phase 1 trial results presented at EANM 2026 evaluated ²²⁵Ac-LNC1011, a PSMA-targeted alpha radioligand chemically modified for extended circulation, in 15 mCRPC patients receiving 3.7 MBq per cycle. An 86.7% PSA50 response rate (13/15) and a 60% PSA90 response rate (9/15) were achieved. Side effects were primarily mild-to-moderate, with dry mouth occurring in 80% of patients.​

​

Preclinical Research & Reviews

• IRONMAN Registry Analysis: Mortality Risk by Age and Epigenetic Markers​
  An observational analysis of 4,332 patients across 15 countries from the IRONMAN registry revealed a J-shaped relationship between chronological age and mortality in advanced prostate cancer. Men diagnosed at age 55 or younger and those aged 80 or older experienced higher mortality rates in both mHSPC and CRPC cohorts. In an exploratory biomarker sub-analysis, accelerated epigenetic aging and high-risk clonal hematopoiesis were also linked to increased mortality rates.​
  ​

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 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