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mCRPCMay 2026
0:00 / 3:24
Metastatic Castration Resistant Prostate Cancer — Monthly Compass
May 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
  • Important Drug Publication Updates
    • KEYNOTE‑641 showed that adding pembrolizumab to enzalutamide did not improve radiographic progression‑free or overall survival and increased grade ≥3 treatment‑related adverse events in mCRPC, not supporting clinical use of this combination.
  • Key Clinical Development Updates
    • Adicet Bio plans a Q3 2026 regulatory filing for ADI‑212, a PSMA‑targeted, gene‑edited and armored allogeneic gamma delta CAR‑T for mCRPC, with first‑in‑human Phase 1 enrollment anticipated in Q4 2026 pending regulatory clearance.
    • Olema and Bayer entered a collaboration to evaluate OP‑3136 (KAT6 inhibitor) plus darolutamide in mCRPC, with a Phase 1b/2 study slated to start in H2 2026 and enabled by prior FDA IND clearance for OP‑3136 and the ongoing Phase 1.
  • Important Clinical Trial Publications
    • KEYNOTE‑365 Cohort E reported that pembrolizumab plus lenvatinib produced modest activity (34% confirmed PSA response; 36% objective response) in docetaxel‑pretreated mCRPC but with a high incidence of treatment‑related adverse events.
    • Integrated single‑cell imaging, therapeutic modeling, and a Phase Ib trial of enzalutamide plus venetoclax validated BCL‑2 as a therapeutic target across heterogeneous castration‑resistant prostate cancer, with AR pathway inhibitors inducing BCL‑2 as a shared vulnerability.
  • Key Conference Updates
    • ASCO 2026 mCRPC data emphasized alpha and non‑PSMA radiotherapeutics (e.g., [225Ac]Ac‑PSMA‑617 in AcTION and B7‑H3 radioconjugate AKY‑2519 with robust tumor uptake and limited normal‑tissue exposure), ADC advances addressing antigen heterogeneity (ABBV‑969 PSMA/STEAP1 bispecific with 45% confirmed ORR and B7‑H3 ADC BNT324/DB‑1311 entering Phase 3 vs docetaxel), and AR‑pathway optimization including darolutamide vs enzalutamide and overall survival benefit for radium‑223 plus enzalutamide in bone‑dominant mCRPC.
  • Emerging Themes & Macro-Trends
    • Development is converging on alpha‑RLT platforms and non‑PSMA targets (notably B7‑H3), bispecific ADCs to overcome antigen heterogeneity, and ARPI portfolio strategies that leverage head‑to‑head data and rational combinations (e.g., KAT6 inhibition with darolutamide) to integrate with radiotherapeutics.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-05-01 and 2026-05-31 about metastatic castration resistant prostate cancer.
Clinical Development Regulatory Updates
Clinical Development Regulatory Updates
  • Adicet Bio reported it is on track to submit a regulatory filing for ADI-212, a PSMA‑targeted, gene‑edited and armored allogeneic gamma delta CAR‑T for metastatic castration‑resistant prostate cancer (mCRPC), in Q3 2026, with Phase 1 enrollment anticipated in Q4 2026 pending regulatory clearance. The company framed ADI‑212 as its next solid‑tumor entry as it advances toward first‑in‑human evaluation. ¹ (businesswire.com) (read more)
  • Olema Oncology announced a clinical trial collaboration and supply agreement with Bayer to evaluate OP‑3136 (KAT6 inhibitor) plus NUBEQA (darolutamide) in mCRPC, with a Phase 1b/2 study planned to start in H2 2026. The company reiterated that the IND for OP‑3136 had been cleared by the FDA (December 2024), enabling the ongoing Phase 1 and this combination study. ² (nasdaq.com) (read more)
Conference
Major Conference Updates
Conference Information
  • ASCO 2026 Annual Meeting, Chicago, Illinois, May 29–June 2, 2026. Momentum in mCRPC centers on radiotherapeutics moving beyond PSMA/Lu‑177, ADC innovation aimed at antigen heterogeneity, and AR‑pathway optimization including head‑to‑head and combination strategies. (read more)
  • Theme 1: Alpha and Non‑PSMA Radiotherapeutics Advance
    • Significance: Alpha emitters and new targets seek to overcome post‑ARPI/chemotherapy resistance and tolerability limits of beta‑emitters, broadening radioligand options beyond PSMA. (read more)
    • Mechanism insights / clinical impact: ^225Ac programs highlight higher linear energy transfer with short path length; AcTION evaluates [225Ac]Ac‑PSMA‑617 in mCRPC with/without prior [177Lu]Lu‑PSMA exposure. B7‑H3 miniprotein radioconjugate AKY‑2519 shows robust tumor uptake with low normal‑tissue (including salivary) exposure, supporting a potentially wider therapeutic index. (read more)
    • Patient populations affected: mCRPC after ARPI and/or prior radioligand therapy; PLUVICTO‑naïve and ‑experienced cohorts now enrolling in dedicated AKY‑2519 Phase 1b. (read more)
  • Theme 2: ADC Innovation—Bispecific and B7‑H3 Strategies
    • Significance: As sequencing after ARPIs, taxanes, and PSMA RLT remains challenging, ADCs are targeting multi‑antigen escape and PSMA‑low disease, with early efficacy that could redefine post‑standard lines. (read more)
    • Mechanism insights / clinical impact: ABBV‑969, a PSMA/STEAP1 bispecific ADC, produced a 45% confirmed ORR (RECIST‑evaluable n=29) with meaningful PSA50/90 responses in heavily pretreated mCRPC; BNT324/DB‑1311 (B7‑H3 ADC) is entering Phase 3 vs docetaxel in taxane‑naïve mCRPC, signaling confidence in a biomarker‑agnostic antigen. (read more)
    • Patient populations affected: Heavily pretreated mCRPC (ABBV‑969) and taxane‑naïve mCRPC (BNT324/DB‑1311), including patients with heterogeneous/low PSMA expression where bispecific or B7‑H3 targeting may expand reach. (read more)
  • Theme 3: AR‑Pathway Optimization and Radiotherapy Combinations
    • Significance: Head‑to‑head ARPI data and alpha‑radiotherapy combinations aim to extend survival while guiding regimen selection and sequencing. (read more)
    • Mechanism insights / clinical impact: ARACOG (AFT‑47) will present darolutamide vs enzalutamide across CRPC settings; final EORTC 1333/PEACE‑3 shows OS benefit adding radium‑223 to enzalutamide in bone‑dominant mCRPC, with practical implications for integrating alpha emitters. (read more)
    • Patient populations affected: Metastatic and non‑metastatic CRPC candidates for ARPIs; bone‑dominant mCRPC suited for radium‑223 plus enzalutamide; future combo exploration includes OP‑3136 (KAT6 inhibitor) with darolutamide in mCRPC. (read more)
  • Significance
    • Expected clinical or translational readouts: Rapid‑oral AcTION results (^225Ac‑PSMA‑617) and first‑in‑human AKY‑2519 dosimetry/imaging guide alpha‑RLT dose design and patient selection; ABBV‑969 expansion cohorts refine durability and safety. (read more)
    • Regulatory or policy implications: Positive alpha‑RLT and ADC signals could catalyze Breakthrough/Fast Track discussions, particularly for post‑RLT or PSMA‑low segments with high unmet need. (read more)
    • Potential shifts in standard of care: Emergence of non‑PSMA (B7‑H3) radiotherapeutics and bispecific ADCs may reshape post‑ARPI/taxane lines; ARPI selection and alpha‑combination (radium‑223 + enzalutamide) could influence frontline mCRPC with bone‑dominant disease. (read more)
    • Strategic implications: Invest in alpha‑RLT platforms and non‑PSMA targets (B7‑H3); accelerate bispecific ADCs addressing antigen heterogeneity; position ARPI portfolios with head‑to‑head and rational combinations (e.g., KAT6 inhibitor + darolutamide) to defend/complement radiotherapeutic adoption. (read more)
Publications Related to Approved Drugs
Phase 3
pembrolizumab
Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer (KEYNOTE-641): a multicentre, randomised, double-blind, phase 3 trial. The phase 3 KEYNOTE-641 trial demonstrated that the addition of pembrolizumab to enzalutamide did not improve radiographic progression-free survival or overall survival in patients with metastatic castration-resistant prostate cancer. Furthermore, the combination was associated with a higher incidence of grade 3 or worse treatment-related adverse events, indicating that this regimen is not supported for clinical use in this patient population. ()
New Publications Related to Drugs in Clinical Trial Development
Phase 3
Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): trial protocols. The MEVPRO-1 and MEVPRO-2 phase III trials are evaluating the efficacy and safety of combining the EZH2 inhibitor mevrometostat with enzalutamide in patients with metastatic castration-resistant prostate cancer. These studies aim to determine if this novel combination can significantly improve radiographic progression-free survival compared to standard therapies in both pretreated and treatment-naïve populations. ()
Phase 2
Efficacy of the ATR Inhibitor Ceralasertib in Patients with ARID1A-Deficient Gynecologic and Other Solid Tumor Malignancies. Ceralasertib monotherapy demonstrated promising antitumor activity in patients with ARID1A-deficient gynecologic malignancies, particularly endometrioid endometrial and ovarian clear-cell carcinomas. Exploratory analyses identified upregulated DNA damage response pathways and immune microenvironment changes as potential biomarkers of response, informing further development of ATR inhibitors in this population. ()
PHASE1, PHASE2
Pembrolizumab Plus Lenvatinib in Participants with Docetaxel-pretreated Metastatic Castration-resistant Prostate Cancer: Results from KEYNOTE-365 Cohort E. The combination of pembrolizumab and lenvatinib demonstrated modest antitumor activity, with a 34% confirmed PSA response rate and a 36% objective response rate, in patients with docetaxel-pretreated metastatic castration-resistant prostate cancer. However, the regimen was associated with a high incidence of treatment-related adverse events, highlighting the need for careful toxicity management in this setting. ()
Phase 1
Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): trial protocols. The MEVPRO-1 and MEVPRO-2 phase III trials are evaluating the efficacy and safety of combining the EZH2 inhibitor mevrometostat with enzalutamide in patients with metastatic castration-resistant prostate cancer. These studies aim to determine if this novel combination can significantly improve radiographic progression-free survival compared to standard therapies in both pretreated and treatment-naïve populations. ()
Phase 3
Phase III randomized studies of mevrometostat and enzalutamide in metastatic prostate cancer (MEVPRO-1 and MEVPRO-2): trial protocols. The MEVPRO-1 and MEVPRO-2 phase III trials are evaluating the efficacy and safety of combining the EZH2 inhibitor mevrometostat with enzalutamide in patients with metastatic castration-resistant prostate cancer. These studies aim to determine if this novel combination can significantly improve radiographic progression-free survival compared to standard therapies in both pretreated and treatment-naïve populations. ()
Phase 1
Single-cell imaging analysis, therapeutic modeling and a Phase Ib trial validate BCL-2 as a target across heterogeneous castration-resistant prostate cancer. Preclinical and clinical studies, including a Phase Ib trial combining enzalutamide and venetoclax, validate BCL-2 as a critical therapeutic target across diverse subtypes of castration-resistant prostate cancer. The selective induction of BCL-2 by androgen receptor pathway inhibitors highlights a shared vulnerability that can be exploited to overcome treatment resistance. ()
Phase 2
Nivolumab plus ipilimumab for chemotherapy-refractory metastatic castration-resistant prostate cancer: results from the randomized portion of the phase 2 CheckMate 650 trial. The combination of nivolumab and ipilimumab demonstrated preliminary antitumor activity in a subset of patients with chemotherapy-refractory metastatic castration-resistant prostate cancer, albeit with significant toxicity. Exploratory biomarker analyses identified a perivascular immune niche transcriptional signature associated with prolonged overall survival, offering a potential tool for patient selection in future immunotherapy trials. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in metastatic castration resistant prostate cancer updated from 2026-05-01 to 2026-05-31:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation1-----1
Not Yet Recruiting233---8
Recruiting1515819149
Available-------
Approved for Marketing-------
Active, Not Recruiting939-6229
Completed--1---1
Total272121115388
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
Prednisone, docetaxel, : lorigerlimab NCT05848011 COMPLETED A Phase 2, Randomized, Open-Label, Study of Lorigerlimab With Docetaxel or Docetaxel Alone in Participants With Metastatic Castration-Resistant Prostate Cancer 2026-03-16
Prednisone, Abiraterone Acetate/Niraparib NCT05689021 ACTIVE_NOT_RECRUITING Phase 2 Study of CJNJ-67652000 (Niraparib/Abiraterone Acetate Fixed-Dose Combination) and Prednisone for Metastatic Castration-Resistant Prostate Cancer Associated With SPOP Mutation With or Without Homologous Recombination Deficiency 2026-07-31
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:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Androgen-deprivation Therapy (ADT), Apalutamide 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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