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mCRPCMarch 2026
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Metastatic Castration Resistant Prostate Cancer — Monthly Compass
Mar 01–31, 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
    • NCCN adopted pre‑taxane 177Lu‑PSMA‑617 for mCRPC, marking a guideline shift that enables earlier‑line PSMA radioligand therapy.
  • Key Clinical Development Updates
    • Telix’s ProstACT Phase 3 of TLX591‑Tx (177Lu‑rosopatamab tetraxetan) met Part 1 safety/dosimetry objectives and will be presented to the FDA to amend the IND and initiate randomized Part 2 in the United States, with ex‑US regions already authorized and advancing.
    • BioNTech advanced its B7‑H3–targeted ADC BNT324/DB‑1311 in mCRPC with updated Phase 1/2 data presented at ASCO GU 2026 and expects to start a Phase 3 trial in 2026, while planning a 2026 BLA for BNT323 subject to FDA feedback.
  • Important Clinical Trial Publications
    • In KEYNOTE‑365 Cohort G (phase 1b/2), vibostolimab coformulated with pembrolizumab showed limited antitumor activity in docetaxel‑pretreated mCRPC despite manageable safety, indicating the need for alternative immunotherapy strategies in this setting.
    • The phase 2 ARROW study showed that adding 131I‑LNTH‑1095 radioligand therapy to enzalutamide significantly increased PSA50 responses versus enzalutamide alone in PSMA‑avid mCRPC, with a higher incidence of grade ≥3 hematologic toxicities.
  • Key Conference Updates
    • EAU26 and PSMA & Beyond 2026 reinforced PSMA radiotherapeutics as foundational in mCRPC, focusing on individualized dosing and sequencing while addressing emerging renal and long‑term marrow toxicities as therapy moves earlier.
    • Sessions emphasized BRCA‑anchored PARP inhibitor use in DDR‑altered mCRPC and reported credible activity for PSMA/STEAP1/hK2‑targeted bispecifics and ADCs that must overcome CRS, hematologic toxicity, logistical, and sequencing challenges versus PSMA RLT.
  • Emerging Themes & Macro-Trends
    • Infrastructure priorities highlighted included scaling PSMA‑PET access, implementing dosimetry‑guided workflows, strengthening renal and marrow monitoring, building BRCA testing pathways, and preparing outpatient CRS management to enable broader bispecific deployment.
    • Anticipated near‑term developments include phase 3 readouts for xaluritamig (NCT06691984) and multiple RLT‑combination efforts, with maturing renal and marrow safety datasets expected to enable dose personalization.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-03-01 and 2026-03-31 about metastatic castration resistant prostate cancer.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Telix Pharmaceuticals reported that Part 1 of its global Phase 3 ProstACT study of TLX591-Tx (177Lu-rosopatamab tetraxetan) in PSMA-positive mCRPC achieved its primary safety/dosimetry objectives; the company will present Part 1 data to the FDA to seek an IND amendment to progress randomized Part 2 in the United States. The release also notes the trial is already advancing in ex-US regions where health authority approvals have been obtained. (globenewswire.com)¹ (read more)
  • BioNTech’s March 10, 2026 corporate update highlighted its B7-H3–targeted ADC BNT324/DB-1311 for mCRPC, noting updated Phase 1/2 data presented at ASCO GU 2026 and that a Phase 3 trial is expected to initiate in 2026; in the same release, BioNTech and DualityBio stated they plan to file a BLA in 2026 for another ADC (BNT323) subject to FDA feedback, indicating ongoing US regulatory interactions. (investors.biontech.de)² (read more)
Conference
Major Conference Updates
Conference Information
  • European Association of Urology Annual Congress (EAU26), London, United Kingdom; March 13–16, 2026. PSMA & Beyond 2026 (UCSF/UCLA/PCF), UCLA Luskin Conference Center, Los Angeles, California; March 26–27, 2026. (read more)
  • Overall sentiment: Radiotherapeutics cement their role in mCRPC while attention shifts to risk-adapted dosing and late toxicities; precision DDR targeting remains BRCA-driven; and bispecifics/ADCs show credible activity but will compete on safety, logistics, and sequencing with PSMA RLT. (read more)
  • Theme 1: PSMA Radiotherapeutics: Optimization, Toxicity, and Patient Selection
    • Significance: mCRPC remains the anchor indication for ^177Lu‑PSMA‑617; March discussions emphasized who benefits, how to individualize dose/sequence, and how to mitigate renal/marrow risks. A validated radium‑223 risk model supports more precise selection in bone‑predominant disease. (read more)
    • Mechanism insights / clinical impact: Beta (Lu‑177) versus alpha (Ac‑225) emitters show distinct toxicity trade‑offs (xerostomia prominent with Ac‑PSMA); renal and long‑term marrow effects are emerging focus areas as RLT moves earlier. Clinical content highlighted low observed late renal toxicity to date, but underscored knowledge gaps and the need for dosimetry‑guided strategies. (read more)
    • Patient populations affected: PSMA‑positive mCRPC across taxane‑naïve and post‑taxane settings; bone‑metastatic mCRPC considered for radium‑223; earlier-line use supported by guideline momentum in pre‑taxane PSMA‑RLT. (read more)
  • Theme 2: DDR-Directed Precision (PARP Inhibitors) in mCRPC
    • Significance: Consensus messaging reinforced that PARP inhibition is most impactful in BRCA1/2‑altered disease and remains a key precision pillar in mCRPC. (read more)
    • Mechanism insights / clinical impact: Trials including PROfound, TRITON3, and TALAPRO‑2 define efficacy across lines and in combination with ARPIs; anemia/neutropenia and transfusion burden remain the differentiating safety costs, highlighting the need for biomarker‑driven use. (read more)
    • Patient populations affected: mCRPC with HRR alterations—especially BRCA1/2—across first‑line and later settings; applicability beyond BRCA remains more limited and toxicity‑constrained. (read more)
    • Significance: Activity signals with T‑cell engagers and ADCs point to credible competition with taxanes and potential combination partners for RLT, provided toxicity and administration hurdles are solved. (read more)
    • Mechanism insights / clinical impact: Agents such as acapatamab, JNJ‑63898081, xaluritamig, and pasritamig demonstrate PSA and ORR signals but carry CRS and hematologic toxicities; target selection (PSMA vs STEAP1 vs hK2) and construct engineering drive differentiation. (read more)
    • Patient populations affected: Heavily pretreated mCRPC (often taxane‑exposed); future biomarker‑enriched cohorts (e.g., STEAP1, hK2) likely to refine positioning. (read more)
  • Significance
    • Expected clinical or translational readouts: Ongoing phase 3 for xaluritamig and multiple RLT‑combination efforts highlighted; anticipate maturation of RLT safety (renal/marrow) datasets that could inform dose personalization. (read more)
    • Regulatory or policy implications: March updates emphasized NCCN adoption of pre‑taxane ^177Lu‑PSMA‑617 in mCRPC and growing integration of PSMA‑PET in trial design. (read more)
    • Potential shifts in standard of care: Movement toward risk‑adapted RLT (including alpha emitters) and continued BRCA‑anchored PARP use; bispecifics/ADCs could displace or combine with taxanes in refractory mCRPC pending phase 3 data. (read more)
    • Strategic implications: Prioritize PSMA‑PET access, dosimetry capability, and renal/marrow monitoring infrastructure; invest in BRCA testing pathways; prepare for outpatient CRS management to enable broader bispecific deployment. (read more)
Publications Related to Approved Drugs
Phase 3
enzalutamide
Radiographic Progression With and Without Prostate-Specific Antigen Rise in Patients With Advanced Prostate Cancer Treated With Enzalutamide. A post hoc analysis of the ARCHES and PROSPER trials reveals that a significant proportion of patients with advanced prostate cancer experience radiographic progression without concurrent PSA rise when treated with enzalutamide plus ADT. Given the poor prognosis associated with this discordance, periodic imaging surveillance is highly recommended to accurately monitor disease progression. (, )
Phase 3
darolutamide
Use of concomitant G-CSF in maintaining efficacious dose and safe delivery of docetaxel in combination with darolutamide in ARASENS: A phase III study. In the phase III ARASENS trial, the appropriate use of concomitant G-CSF and docetaxel dose modifications enabled over 97% of patients to receive an efficacious dose of docetaxel alongside darolutamide and ADT. This proactive management strategy effectively mitigates neutropenic complications, ensuring safe and sustained delivery of the triplet therapy regimen. ()
Phase 3
enzalutamide
Enzalutamide in patients with high-risk biochemically recurrent prostate cancer according to the European Association of Urology definition: a post hoc analysis of EMBARK. A post hoc analysis of the EMBARK trial demonstrates that enzalutamide, both as a monotherapy and in combination with leuprolide, significantly improves metastasis-free survival compared to leuprolide alone in patients with high-risk biochemically recurrent prostate cancer. These findings validate the efficacy and safety of enzalutamide regimens specifically within the European Association of Urology-defined high-risk patient population. ()
New Publications Related to Drugs in Clinical Trial Development
PHASE1, PHASE2
Vibostolimab Coformulated with Pembrolizumab in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: KEYNOTE-365 Cohort G. The phase 1b/2 KEYNOTE-365 Cohort G study demonstrated that the combination of vibostolimab and pembrolizumab had limited antitumor activity in patients with docetaxel-pretreated metastatic castration-resistant prostate cancer, despite a manageable safety profile. These findings suggest that alternative immunotherapeutic strategies or combinations may be required to overcome resistance in this heavily pretreated population. ()
Phase 3
Steroidogenesis inhibitor opevesostat (MK-5684) for metastatic castration-resistant prostate cancer: OMAHA-003 and OMAHA-004 trial designs. The randomized phase III OMAHA-003 and OMAHA-004 trials are designed to evaluate the efficacy and safety of the novel steroidogenesis inhibitor opevesostat compared to an androgen receptor pathway inhibitor switch in previously treated metastatic castration-resistant prostate cancer. This approach aims to overcome resistance driven by androgen receptor-ligand-binding domain mutations, potentially establishing opevesostat as a critical next-generation therapeutic option. (, )
Phase 2
Clinical Utility of Transcriptomic Signatures to Identify Androgen Receptor and Neuroendocrine Signaling in Prostate Cancer. A large-scale transcriptomic analysis identified four distinct molecular subtypes of prostate cancer based on androgen receptor and neuroendocrine signaling, revealing that tumors with high androgen receptor signaling exhibit significantly longer overall survival compared to those with neuroendocrine features. This molecular stratification provides a robust framework for precision oncology, informing patient selection for biomarker-driven therapies in ongoing trials. ()
Phase 2
131I-LNTH-1095 Radioligand Therapy Plus Enzalutamide vs. Enzalutamide Alone in Men With PSMA-Avid Metastatic Castration-Resistant Prostate Cancer: A Phase 2 Study. The phase 2 ARROW study revealed that combining 131I-LNTH-1095 radioligand therapy with enzalutamide significantly improved PSA50 response rates compared to enzalutamide alone in patients with PSMA-avid metastatic castration-resistant prostate cancer. Although the combination therapy increased the incidence of grade ≥3 hematologic toxicities, the enhanced biochemical response highlights the potential of integrating targeted radioligands with androgen receptor inhibitors. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in metastatic castration resistant prostate cancer updated from 2026-03-01 to 2026-03-31:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting11----2
Recruiting1491217144
Available-------
Approved for Marketing-------
Active, Not Recruiting10-10-6228
Completed2-----2
Total271022113376
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
LHRH agonist/antagonist, Abemaciclib, Darolutamide NCT05999968 COMPLETED A Phase 1b Study of Abemaciclib Plus Darolutamide in Men With Metastatic Castration-Resistant Prostate Cancer 2026-01-21
Dexamethasone, Opevesostat, Fludrocortisone, Hydrocortisone NCT06136598 COMPLETED A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in China Participants With Metastatic Castration-Resistant Prostate Cancer 2026-03-09
Dexamethasone, Fludrocortisone acetate, Opevesostat, Hydrocortisone NCT06104449 ACTIVE_NOT_RECRUITING A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) 2026-04-20
Nivolumab, Radium-223 NCT04109729 ACTIVE_NOT_RECRUITING A Phase IB Study of Nivolumab in Combination With Radium-223 in Men With Metastatic Castration Resistant Prostate Cancer 2026-04-30
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Prednisone, docetaxel, : lorigerlimab NCT05848011 ACTIVE_NOT_RECRUITING A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer 2026-03
Apalutamide, Golimumab NCT05960578 ACTIVE_NOT_RECRUITING TRAMP: Tumor Necrosis Factor- α Blockade and AR Inhibition in Men With CRPC 2026-04-07
AAA617, 68Ga-PSMA-11 NCT06004661 RECRUITING An Open-label Dosimetry, Biodistribution, Tolerability and Safety Study of Lutetium (177Lu) Vipivotide Tetraxetan in Participants With Progressive PSMA-Positive Metastatic Castration-Resistant Prostate Cancer (mCRPC) With Moderately and Severely Impaired and With Normal Renal Function. 2026-06-17
Tuvusertib NCT05828082 ACTIVE_NOT_RECRUITING A Phase 2 Study of M1774 in Refractory SPOP-Mutant Prostate Cancer 2026-06-18
Phase 3 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
abiraterone acetate, olaparib NCT05171816 ACTIVE_NOT_RECRUITING A Randomised, Double-blind, Placebo-controlled, Multicentre Phase III Study of Olaparib Plus Abiraterone Relative to Placebo Plus Abiraterone as First-line Therapy in Men With Metastatic Castration-resistant Prostate Cancer (PROpel Study) 2026-04-28
Phase 4 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Apalutamide, Androgen-deprivation Therapy (ADT) NCT04108208 ACTIVE_NOT_RECRUITING A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Phase IV Study of Apalutamide in Chinese Participants With Non-Metastatic Castration-Resistant Prostate Cancer (NM-CRPC) 2026-06-05
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