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mCRPCJune 2026
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Metastatic Castration Resistant Prostate Cancer — Monthly Compass
Jun 01–30, 2026 • Priority Updates • 3–5 minute read
 
A curated, practice-minded digest of what moved in metastatic castration resistant prostate cancer this month — regulatory signals, clinical development, and the most practice-relevant publications.
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metastatic castration resistant prostate cancer updates
Key Highlights
Key Highlights
  • Practice-Changing Updates
    • On June 1, 2026, the FDA approved FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostics to identify HRR gene–mutated mCRPC patients eligible for talazoparib plus enzalutamide, expanding Foundation Medicine’s FDA‑approved CDx indications and directly linking testing to an FDA‑approved combination therapy in mCRPC.
  • Key Clinical Development Updates
    • Telix reported Part 1 results of the phase 3 ProstACT Global study of TLX591‑Tx (177Lu‑rosopatamab tetraxetan) in mCRPC and is engaging the FDA to seek an IND amendment to progress Part 2 in the United States while Part 2 enrollment continues in jurisdictions with regulatory approval.
    • BioNTech/DualityBio advanced the taxane‑naïve mCRPC program with the phase 3 BNT324‑03 trial randomizing the B7‑H3 ADC BNT324/DB‑1311 versus docetaxel, supported by its prior FDA Fast‑Track Designation for previously treated castration‑resistant prostate cancer.
  • Key Conference Updates
    • At ASCO 2026, alpha‑emitting PSMA radioligands (225Ac‑PSMA‑617, 225Ac‑rosopatamab, 225Ac‑PSMA‑XT) demonstrated phase 1 activity in PSMA‑positive mCRPC including Lu‑PSMA–pretreated cohorts, and beta‑emitter analyses clarified transient PSA flare and real‑world sequencing versus docetaxel to refine response assessment and placement.
    • ASCO presentations highlighted bispecific T‑cell engagers moving into AR‑backbone combinations (xaluritamig plus abiraterone in chemo‑naïve mCRPC with a global phase 3 randomization against investigator’s choice) and the emergence of dual‑target PSMA/STEAP1 ADCs like ABBV‑969 carrying a TOP1 payload for heavily pretreated antigen‑positive disease.
  • Emerging Themes & Macro-Trends
    • Near‑term inflection points include phase 3 readouts for alpha‑RLT (AcTFirst) and xaluritamig+abiraterone (XALience) alongside ABBV‑969 expansion cohorts and additional alpha‑RLT phase 1 updates.
    • Strategic priorities crystallized around securing actinium‑225 supply, advancing STEAP1/PSMA co‑targeting portfolios, and deploying companion liquid assays for patient selection, response monitoring, and payer alignment to accelerate RLT and ADC adoption.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • On June 12, 2026, the FDA approved capivasertib (Truqap, AstraZeneca) in combination with abiraterone and prednisone for adults with metastatic androgen pathway modulation-naïve or -sensitive prostate cancer that is PTEN-deficient. The approval was based on efficacy data from the CAPItello-281 trial, which demonstrated a statistically significant improvement in radiographic progression-free survival. The VENTANA PTEN (SP218) RxDx Assay was also approved as a companion diagnostic to identify eligible patients.¹ (read more)
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Foundation Medicine announced FDA approvals for FoundationOne CDx and FoundationOne Liquid CDx as companion diagnostics to identify homologous recombination repair (HRR) gene–mutated metastatic castration-resistant prostate cancer (mCRPC) patients eligible for TALZENNA (talazoparib) plus XTANDI (enzalutamide). The June 1, 2026 decision expands Foundation Medicine’s FDA‑approved CDx indications in prostate cancer and links testing directly to an FDA‑approved combination therapy in mCRPC. (foundationmedicine.com)¹ (read more)
  • Telix Pharmaceuticals reported Part 1 results from the ProstACT Global phase 3 study of TLX591‑Tx (177Lu‑rosopatamab tetraxetan) in mCRPC and stated it is engaging with the FDA to seek an IND amendment to progress Part 2 of the study in the United States. The company noted Part 2 is already enrolling in jurisdictions where regulatory approvals have been granted, highlighting the ongoing FDA interaction on U.S. trial expansion. (telixpharma.com)² (read more)
  • A Journal of Clinical Oncology ASCO 2026 abstract detailed the phase 3 BNT324‑03 study of BioNTech/DualityBio’s B7‑H3 ADC BNT324/DB‑1311 in taxane‑naïve mCRPC and specified the agent previously received FDA Fast‑Track Designation for previously treated castration‑resistant prostate cancer. The abstract underscores the regulatory status while outlining the randomized design versus docetaxel in this population. (ascopubs.org)³ (read more)
Conference
Major Conference Updates
Conference Information
  • American Society of Clinical Oncology (ASCO) Annual Meeting; Chicago, IL; May 29–June 2, 2026. (read more)
  • Overall sentiment: Clear momentum toward PSMA-directed radiotherapeutics (including alpha emitters), first clinical signals for dual-target ADCs, and acceleration of T‑cell engagers into AR‑backbone combinations, with parallel advances in liquid‑biomarker–guided treatment selection. (read more)
  • Theme 1: Alpha/Beta PSMA Radiotherapeutics Scale-Up
    • Significance: Alpha-emitters are moving from concept to competitive programs alongside maturing beta-emitters, with designs aimed at earlier use and combination backbones—positioning PSMA RLT beyond salvage. (read more)
    • Mechanism insights / clinical impact: High‑LET alpha agents (e.g., 225Ac‑PSMA‑617; 225Ac‑rosopatamab; 225Ac‑PSMA‑XT) reported phase 1 activity in PSMA‑positive mCRPC, including Lu‑PSMA–pretreated cohorts; beta‑emitter data emphasized PSA flare dynamics and real‑world sequencing versus docetaxel, informing response assessment and placement. (read more)
    • Patient populations affected: PSMA‑PET–positive mCRPC, including post‑ARPI and post‑Lu‑PSMA settings; phase 3 (AcTFirst) testing alpha‑RLT plus ARPI aims to expand earlier‑line access. (read more)
  • Theme 2: T‑Cell Engagers + AR Pathway Backbones
    • Significance: Bispecific T‑cell engagers are transitioning from monotherapy signals to combination strategies with abiraterone, targeting chemo‑naïve mCRPC and setting up registrational paths. (read more)
    • Mechanism insights / clinical impact: Xaluritamig (STEAP1×CD3) leverages lineage‑restricted STEAP1 to recruit cytotoxic T cells; combination with abiraterone seeks deeper, more durable responses with manageable immune toxicities versus systemic chemotherapy. (read more)
    • Patient populations affected: Chemotherapy‑naïve mCRPC progressing after prior ARPI exposure; global phase 3 (XALience) randomizes xaluritamig+abiraterone versus investigator’s choice (docetaxel/cabazitaxel/abiraterone). (read more)
  • Theme 3: Dual‑Target ADCs Against PSMA/STEAP1
    • Significance: ADCs are entering prostate cancer with designs to mitigate antigen heterogeneity and deliver potent DNA‑damaging payloads; early signals could open a chemotherapy‑like but targeted option after ARPIs/RLT. (read more)
    • Mechanism insights / clinical impact: ABBV‑969 is a first‑in‑human PSMA/STEAP1 dual‑target ADC carrying a topoisomerase‑1 inhibitor payload—an approach that may retain activity despite variable antigen density and differentiate via bystander effect/toxicity profile typical of TOP1‑payload ADCs. (read more)
    • Patient populations affected: Heavily pretreated mCRPC; antigen‑positive disease irrespective of HRR status, with potential expansion if durability and tolerability hold in dose‑expansion. (read more)
  • Theme 4: Liquid Biomarkers to Guide Selection and Sequencing
    • Significance: Trials increasingly embed ctDNA and blood‑based transcript assays to personalize therapy and optimize RLT/chemotherapy sequencing. (read more)
    • Mechanism insights / clinical impact: PROTRACT tests ctDNA‑guided biomarker‑directed therapy versus clinician’s choice post‑abiraterone; early PROSTest changes predict outcomes to 177Lu‑PSMA and chemotherapy, enabling earlier go/no‑go decisions. (read more)
    • Patient populations affected: Post‑abiraterone mCRPC and candidates for PSMA‑RLT or chemotherapy across geographies adopting blood‑based testing. (read more)
  • Significance
    • Expected clinical or translational readouts: Phase 3 alpha‑RLT (AcTFirst) and xaluritamig+abiraterone (XALience) readouts; ABBV‑969 expansion cohorts; additional alpha‑RLT phase 1 updates. (ascopubs.org) (read more)
    • Regulatory or policy implications: Potential label expansions for PSMA RLT earlier lines; evolving guidance on PSA flare interpretation and imaging‑based endpoints in RLT studies. (ascopubs.org) (read more)
    • Potential shifts in standard of care: AR‑backbone combinations with T‑cell engagers; movement of alpha‑RLT into ARPI‑treated chemo‑naïve mCRPC; biomarker‑directed sequencing. (ascopubs.org) (read more)
    • Strategic implications: Secure actinium‑225 supply chains; prioritize STEAP1/PSMA co‑targeting portfolios; invest in companion liquid assays to enable selection, response monitoring, and payer alignment for RLT and ADC adoption. (ascopubs.org) (read more)
Publications Related to Approved Drugs
Phase 3
darolutamide
Clinically relevant endpoints and quality-of-life outcomes with darolutamide in patients with metastatic hormone-sensitive prostate cancer: Analyses of the phase III ARASENS trial. In the ARASENS trial, adding darolutamide to androgen deprivation therapy (ADT) and docetaxel significantly delayed time to metastatic castration-resistant prostate cancer (mCRPC) and pain progression versus placebo with ADT and docetaxel. This triplet therapy maintained health-related quality of life with no cumulative adverse events over long-term follow-up, reinforcing its position as a standard-of-care treatment for patients with metastatic hormone-sensitive prostate cancer (mHSPC). () .
Phase 3
talazoparib
Exposure-safety analyses of talazoparib in combination with enzalutamide in patients with metastatic castration-resistant prostate cancer (mCRPC) in the TALAPRO-2 trial. This exposure-safety analysis of the TALAPRO-2 trial established a relationship between higher talazoparib exposure and increased risk of Grade ≥3 anemia, thrombocytopenia, and neutropenia in mCRPC patients. The findings validate the study's dose modification algorithm as an effective strategy for managing the hematologic adverse events associated with the talazoparib plus enzalutamide combination. () .
Phase 3
enzalutamide
Enzalutamide in biochemically recurrent prostate cancer: clinical implications from EMBARK for real-world practice. In a podcast discussion, investigators from the phase III EMBARK trial reviewed the real-world implications of their findings, where enzalutamide with or without leuprolide significantly improved metastasis-free survival over leuprolide alone in patients with high-risk biochemically recurrent prostate cancer. The discussion highlights that the enzalutamide combination also led to a significant overall survival benefit, maintained quality of life, and is applicable regardless of primary therapy, supporting its use in this setting. () .
Phase 3
olaparib
First Real-World Data of Olaparib Combination Treatment with Abiraterone and Prednisone or Prednisolone in First-Line Metastatic Castration-Resistant Prostate Cancer (mCRPC): Descriptive Analysis of 154 Patients Enrolled in the Early Access Program in France. The first real-world data from a French early access program confirms that the characteristics and safety profile of patients receiving first-line olaparib plus abiraterone for mCRPC are consistent with those in the pivotal PROpel trial. No new safety signals were reported, supporting the positive benefit-risk balance of this combination in a real-world population, including those with unknown homologous recombination repair (HRR) gene mutation status. () .
Phase 3
enzalutamide
Enzalutamide in biochemically recurrent prostate cancer: key findings from subsequent analyses of EMBARK and their implications in clinical practice. This podcast with EMBARK investigators delves into subsequent analyses of the trial, confirming the meaningful improvement in overall survival with the enzalutamide plus leuprolide combination versus leuprolide alone for high-risk biochemically recurrent prostate cancer. The discussion focuses on the real-world clinical implications of secondary endpoints and patient-reported outcomes, reinforcing the combination's efficacy and quality-of-life benefits. () .
Phase 3
abiraterone acetate
Association between concomitant ACEI/ARBs use and survival of patients with prostate cancer receiving abiraterone acetate: A post-hoc analysis of two randomized trials. A post-hoc analysis of the COU-AA-301 and COU-AA-302 trials revealed that concomitant use of ACE inhibitors or angiotensin receptor blockers (ACEI/ARBs) was associated with longer radiographic progression-free survival (rPFS), overall survival (OS), and prostate cancer-specific survival (PCSS) in patients receiving abiraterone acetate. These findings suggest a potential synergistic benefit of ACEI/ARB-containing antihypertensive regimens that warrants further investigation. () .
New Publications Related to Drugs in Clinical Trial Development
Phase 2
Genetic ancestry-concordant ceramide metabolism and response to androgen receptor pathway inhibition in metastatic castration-resistant prostate cancer. This study identified that ceramide metabolites differ between Black and White patients with mCRPC and are associated with clinical outcomes following treatment with androgen receptor pathway inhibitors (ARPI). These findings suggest that specific ceramide profiles, which vary by genetic ancestry, could serve as predictive biomarkers for ARPI response and survival, highlighting a novel metabolic strategy to understand racial disparities in treatment efficacy. (, )
Phase 2
Exploratory FDG PET/CT Imaging in mCRPC Patients Treated with Sipuleucel-T ± IL-7: A Phase II Trial Subanalysis. This exploratory case series demonstrates the potential utility of [18F]-FDG PET/CT imaging to noninvasively monitor metabolic changes in tumors and immune organs in mCRPC patients receiving sipuleucel-T immunotherapy. The observed changes in metabolic activity correlated with clinical outcomes in individual cases, suggesting that this imaging modality could provide early insights into the biological effects of immunotherapy and warrants validation in larger trials. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in metastatic castration resistant prostate cancer updated from 2026-06-01 to 2026-06-30:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting--1---1
Recruiting945---18
Available-------
Approved for Marketing-------
Active, Not Recruiting3-5---8
Completed--2---2
Total12413---29
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
No phase 1 trials completing within the next three months.
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
68Ga-PSMA-11, [177Lu]Lu-PSMA-617 NCT05670106 COMPLETED A Prospective, Open-label, Multi-center, Single-arm, Phase II Study to Evaluate the Efficacy, Safety, Pharmacokinetics and Dosimetry of [177Lu]Lu-PSMA-617 in Chinese Adult Male Patients With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) 2026-04-22
Enzalutamide, Darolutamide NCT04335682 COMPLETED A Randomized Phase II Study of Androgen Receptor Directed Therapy on COGnitive Function in Patients Treated With Darolutamide or Enzalutamide (ARACOG) 2026-05-01
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
No phase 3 trials completing within the next three months.
Phase 4 Clinical Trials within 3 Months of Primary Completion Date:
No phase 4 trials completing within the next three months.
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