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mCRPCApril 2026
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Metastatic Castration Resistant Prostate Cancer — Monthly Compass
Apr 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
  • Important Drug Publication Updates
    • In the Asian subgroup of MAGNITUDE, first-line niraparib plus abiraterone acetate and prednisone significantly improved radiographic progression-free survival versus placebo in BRCA-mutated mCRPC, confirming clinically relevant benefit with a manageable safety profile consistent with the global population.
    • Real-world data from 154 patients in a French Early Access program showed first-line olaparib combined with abiraterone and prednisone/prednisolone was feasible and safe regardless of homologous recombination repair status, with no new safety signals and a profile aligned with PROpel.
  • Key Clinical Development Updates
    • Janux dosed the first participant in the phase 1 study of JANX014, a double-masked PSMA-directed T-cell engager designed to mitigate cytokine release syndrome, Johnson & Johnson announced two phase 3 TIPS for the KLK2×CD3 bispecific pasritamig at ASCO 2026, and Convergent Therapeutics slated phase 2 CONV01-α (225Ac‑PSMA) data for presentation at ASCO 2026 in Lu‑PSMA–pretreated mCRPC.
  • Important Clinical Trial Publications
    • A CABASTY post hoc analysis validated the cabascore to stratify mCRPC and demonstrated that cabazitaxel significantly improved overall survival versus a second-line androgen receptor pathway inhibitor specifically in the favorable-prognosis subgroup.
    • The randomized phase III HC‑1119‑04 trial found that deutenzalutamide significantly prolonged radiographic progression-free survival with a potential overall survival benefit and a favorable safety profile, notably without seizures or falls, in mCRPC progressing after abiraterone and docetaxel.
  • Key Conference Updates
    • At AACR 2026 and IPCS 2026, radioligand therapy prioritized organ-sparing, stage-tailored deployment with TLX597‑Tx showing low salivary and kidney uptake and antibody-based TLX591‑Tx positioned for mCRPC while the non‑PSMA alpha construct ATNM‑400 showed activity in PSMA‑low/negative models, PSMA‑targeted Amanitin ADC HDP‑103 outperformed an exatecan ADC comparator in heterogeneous PSMA and del(17p) mCRPC PDX, and AR/epigenetic strategies including rinzimetostat and the ARON degrader FX‑111 targeted resistance beyond classic AR antagonism.
  • Emerging Themes & Macro-Trends
    • Regulatory and policy trajectories emphasized organ-dosimetry–driven radioligand protocols with standardized companion imaging, cytokine-release–syndrome mitigation frameworks for T-cell engagers, and hepatic/renal monitoring guidance for Amanitin‑payload ADCs.
    • Strategic priorities highlighted PSMA‑low/negative populations for non‑PSMA alpha radioligands, investment in KLK2/CD3 and tumor‑activated T-cell engager platforms, PSMA‑ADC alliances to address heterogeneity, and combination development pairing PRC2 or AR degradation approaches with AR pathway inhibitors.
FDA Approvals/Withdrawals
FDA Approvals/Withdrawals
  • There are no press releases between 2026-04-01 and 2026-04-30 about metastatic castration resistant prostate cancer.
Publications Related to Approved Drugs
Phase 3
cabazitaxel
Integrated Prognostic Score in Metastatic Castration-resistant Prostate Cancer Treated with Cabazitaxel - A CABASTY Post Hoc Analysis Validated by Two International Prospective Phase 3 Trials. A novel prognostic and predictive tool, the cabascore, was developed and validated to guide treatment sequencing in metastatic castration-resistant prostate cancer (mCRPC). The score successfully stratifies patients into favorable, intermediate, and poor prognostic groups, demonstrating that cabazitaxel significantly improves overall survival compared to a second-line androgen receptor pathway inhibitor specifically in the favorable prognosis subgroup. ()
Phase 3
enzalutamide
Enzalutamide Monotherapy for the Treatment of Prostate Cancer With High-Risk Biochemical Recurrence: EMBARK Secondary End Points. Secondary endpoint analysis of the phase 3 EMBARK trial demonstrates that enzalutamide monotherapy significantly improves time to distant metastasis, symptomatic progression, and first symptomatic skeletal event compared to leuprolide alone in patients with high-risk biochemical recurrence. Furthermore, enzalutamide monotherapy better preserved sexual health, supporting its role as an effective and tolerable alternative to traditional androgen deprivation therapy. ()
Phase 4
cabazitaxel
Integrated Prognostic Score in Metastatic Castration-resistant Prostate Cancer Treated with Cabazitaxel - A CABASTY Post Hoc Analysis Validated by Two International Prospective Phase 3 Trials. A novel prognostic and predictive tool, the cabascore, was developed and validated to guide treatment sequencing in metastatic castration-resistant prostate cancer (mCRPC). The score successfully stratifies patients into favorable, intermediate, and poor prognostic groups, demonstrating that cabazitaxel significantly improves overall survival compared to a second-line androgen receptor pathway inhibitor specifically in the favorable prognosis subgroup. ()
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. Initial real-world data from a French Early Access program confirms the safety and feasibility of first-line olaparib combined with abiraterone and prednisone/prednisolone in patients with mCRPC, regardless of homologous recombination repair mutation status. The patient characteristics and safety profile align with the pivotal PROpel trial, with no new safety signals identified, supporting the continued use of this combination in clinical practice. ()
New Publications Related to Drugs in Clinical Trial Development
Phase 3
Niraparib With Abiraterone Acetate Plus Prednisone as First-Line Therapy in Patients With Metastatic Castration-Resistant Prostate Cancer With Homologous Recombination Repair Gene Alterations: Final Analysis of the Asian Subgroup From the MAGNITUDE Study. In the Asian subgroup of the MAGNITUDE trial, first-line treatment with niraparib plus abiraterone acetate and prednisone significantly improved radiographic progression-free survival compared to placebo in patients with BRCA-mutated metastatic castration-resistant prostate cancer. These findings confirm that the clinically relevant benefits and manageable safety profile observed in the global population extend to Asian patients, supporting this combination as a standard of care for this molecularly defined subgroup. ()
Phase 3
Deutenzalutamide, a novel androgen receptor inhibitor, after progression on docetaxel and abiraterone in metastatic castration-resistant prostate cancer: results from the randomized phase III HC-1119-04 trial. Deutenzalutamide, a novel androgen receptor inhibitor with improved pharmacokinetics, significantly prolonged radiographic progression-free survival and demonstrated a potential overall survival benefit in patients with metastatic castration-resistant prostate cancer who progressed on abiraterone and docetaxel. The treatment exhibited a favorable safety profile, notably without reports of seizures or falls, positioning it as a promising new therapeutic option in this heavily pretreated population. ()
Phase 2
WOMBAT (ANZUP 2201): A Phase 2, Single-arm Study of Bipolar Androgen Therapy in Patients with Nonmetastatic Castration-resistant Prostate Cancer with Prostate-specific Antigen Progression on Darolutamide. The WOMBAT phase 2 trial is investigating the efficacy of bipolar androgen therapy (BAT) to resensitize tumors to darolutamide in patients with nonmetastatic castration-resistant prostate cancer experiencing biochemical progression. By cycling high-dose testosterone with intermittent darolutamide, this novel strategy aims to delay metastasis and alleviate the cumulative toxicities of long-term androgen deprivation, potentially establishing a new treatment paradigm. ()
Phase 2
Phase 2 trial of pTVG-HP ± pTVG-AR DNA vaccines and pembrolizumab in patients with metastatic, castration-resistant prostate cancer (mCRPC). A phase 2 trial evaluating the combination of DNA vaccines (pTVG-HP with or without pTVG-AR) and pembrolizumab in metastatic castration-resistant prostate cancer demonstrated anti-tumor activity, including PSA declines and objective responses. However, the addition of the pTVG-AR vaccine did not significantly enhance clinical efficacy and was associated with a slight increase in toxicity, suggesting that broadening the T-cell response with this specific dual-vaccine approach may not provide additional benefit. ()
PHASE1, PHASE2
[177Lu]Lu-PSMA-617 in combination with pembrolizumab for treatment of metastatic castration resistant prostate cancer (PRINCE): a single-arm, phase 1b/2 study. The combination of [177Lu]Lu-PSMA-617 radioligand therapy and pembrolizumab demonstrated encouraging clinical activity, with a 76% PSA response rate, in patients with metastatic castration-resistant prostate cancer. The safety profile was manageable and consistent with the known toxicities of each agent, suggesting this combination may offer durable clinical benefit for a subset of patients and warrants further investigation. ()
Clinical Trials
Clinical Trials Summary
Number of Clinical Trials in metastatic castration resistant prostate cancer updated from 2026-04-01 to 2026-04-30:
Phase 1Phase 1/2Phase 2Phase 2/3Phase 3Phase 4Total
Enrolling by Invitation-------
Not Yet Recruiting2-1---3
Recruiting12171014-44
Available-------
Approved for Marketing-------
Active, Not Recruiting921114330
Completed2-1---3
Total25192328380
Phase 1 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
Bridging Therapy, JNJ-75229414 NCT05022849 COMPLETED A Phase 1, Dose Escalation Study of JNJ-75229414, a Chimeric Antigen Receptor T Cell (CAR-T) Therapy Directed Against KLK2 for Metastatic Castration-Resistant Prostate Cancer 2026-03-11
Dexamethasone, Hydrocortisone, Fludrocortisone acetate, Opevesostat NCT06104449 COMPLETED A Phase 1 Clinical Study to Investigate the Safety and Pharmacokinetics of MK-5684 in Japanese Participants With Metastatic Castration-resistant Prostate Cancer (mCRPC) 2026-04-17
Phase 2 Clinical Trials within 3 Months of Primary Completion Date:
DRUGNCTIDStatusClinical Trial NameCompletion Date
: lorigerlimab, docetaxel, Prednisone 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
Cabazitaxel, Androgen deprivation therapy, Abiraterone Acetate, Prednisone NCT03419234 ACTIVE_NOT_RECRUITING Cabazitaxel With Abiraterone Versus Abiraterone Alone Randomized Trial for Extensive Disease Following Docetaxel: The CHAARTED2 Trial 2026-04-01
Cediranib, Olaparib NCT02893917 ACTIVE_NOT_RECRUITING A Randomized Phase 2 Study of Cediranib in Combination With Olaparib Versus Olaparib Alone in Men With Metastatic Castration Resistant Prostate Cancer 2026-06-18
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:
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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