Metastatic Castration-Resistant Prostate Cancer (mCRPC) Clinical Trials Recruiting Now (October 2026): PSMA Radioligands, PARP, Next-Gen AR, Cell Therapy

Last updated: October 21, 2026

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What "mCRPC" Means

Prostate cancer is castration-resistant when it keeps growing — a rising PSA and/or new or enlarging metastases — despite hormone therapy (ADT) that has lowered testosterone to castrate levels (below 50 ng/dL). Metastatic means it has spread beyond the prostate, most commonly to bone and lymph nodes, sometimes to liver or lung. Put together, mCRPC is cancer that is both spread and no longer controlled by lowering testosterone alone.

mCRPC is a distinct setting from hormone-sensitive (mHSPC), non-metastatic castration-resistant (nmCRPC), or localized prostate cancer — the approved drugs and the open trials differ. This page focuses only on the metastatic castration-resistant setting. For the full disease picture across all stages, see the main prostate cancer trials page.

Approved Options Today (Before or Alongside a Trial)

Knowing the current standard of care helps you weigh a trial against it. ADT (testosterone suppression) continues throughout mCRPC; the options below are layered on top of it. The right sequence depends on your symptoms, prior therapy, where the cancer has spread, and your biomarkers.

Androgen-receptor signaling inhibitors (ARSIs). Enzalutamide, abiraterone (+ prednisone), darolutamide, and apalutamide further block the androgen-receptor pathway. One ARSI is a common first step in mCRPC; switching to a second ARSI after the first fails gives smaller benefit, which is part of why PSMA radioligand and other mechanisms are moving earlier.
Taxane chemotherapy. Docetaxel is a standard option in mCRPC; cabazitaxel is used after docetaxel. Chemotherapy is often favored when disease is rapidly progressing, symptomatic, or visceral.
Pluvicto (177Lu-PSMA-617) — for PSMA-positive disease. A radioligand that delivers radiation to PSMA-expressing cells. FDA-approved for PSMA-positive mCRPC; approved use follows an ARSI and a taxane, with data now also supporting the post-ARSI, taxane-naive setting (see the evidence below). Requires a PSMA-PET scan to confirm PSMA positivity.
Radium-223 (Xofigo). A bone-seeking radiopharmaceutical for symptomatic bone metastases without visceral disease; improves survival and delays skeletal events.
Sipuleucel-T (Provenge). An autologous cellular immunotherapy for asymptomatic or minimally symptomatic mCRPC.
PARP inhibitors (olaparib, rucaparib) — for HRR/BRCA-mutated tumors; and pembrolizumab for the small subset that is MSI-high/dMMR. These are biomarker-defined — see below.

The Evidence Behind Pluvicto (177Lu-PSMA-617)

PSMA radioligand therapy is the newest pillar of mCRPC treatment. Three trials anchor it, all in PSMA-positive disease:

VISION (Phase 3, approval basis) — 177Lu-PSMA-617 + standard care vs. standard care, in PSMA-positive mCRPC after an ARSI and taxane chemotherapy:

Overall survival: median 15.3 vs. 11.3 months (hazard ratio 0.62)
Radiographic progression-free survival: median 8.7 vs. 3.4 months (hazard ratio 0.40)

TheraP (Phase 2, randomized vs. chemotherapy) — 177Lu-PSMA-617 vs. cabazitaxel in PSMA-positive mCRPC after docetaxel: PSA response (≥50% decline) 66% vs. 37%, with fewer grade 3–4 adverse events.

PSMAfore (Phase 3, earlier line) — 177Lu-PSMA-617 vs. switching to a second ARSI, in PSMA-positive mCRPC after one ARSI and before chemotherapy: radiographic PFS median 9.3 vs. 5.6 months (hazard ratio 0.41); overall survival was not significantly improved, with high crossover to the radioligand noted.

Sources: VISION (Sartor et al., N Engl J Med 2021, NCT03511664); TheraP (Hofman et al., Lancet 2021, NCT03392428); PSMAfore (Sartor et al., Lancet 2024, NCT04689828). Pluvicto is FDA-approved for PSMA-positive mCRPC; eligibility depends on a PSMA-PET scan. Trial results describe PSMA-positive populations and specific prior-treatment settings and may not apply to every patient.

Biomarkers That Open Trial Doors

Many of the most promising mCRPC trials only enroll patients with a specific biomarker. Ask your oncologist which of these you have been tested for — they determine which trials below you can join.

PSMA-PET positivity. A PSMA-PET scan (tracers such as 68Ga-PSMA-11 or 18F-piflufolastat) shows whether your tumor expresses PSMA. It is the gatekeeper for 177Lu-PSMA-617 (Pluvicto) and for most PSMA radioligand and PSMA-targeted cell-therapy trials — the single most important imaging biomarker in mCRPC.
HRR / BRCA1/2 mutations. Roughly a quarter of mCRPC tumors carry homologous-recombination-repair gene mutations (including BRCA1/2, ATM, PALB2, CDK12). They predict benefit from PARP inhibitors and open biomarker-selected trials. Both germline and tumor (somatic) testing are standard — ask whether you have had both.
MSI-high / dMMR. A small subset of tumors have microsatellite instability or mismatch-repair deficiency, which can open immunotherapy (pembrolizumab) options and trials.
AR-V7 and prior-therapy history. The AR-V7 splice variant is associated with resistance to ARSIs and can favor a taxane or a non-AR mechanism. Your exact prior therapies (which ARSI, whether you've had a taxane) also define eligibility for most trials below.

Recruiting Trials by Mechanism

The mCRPC landscape in 2026 is led by PSMA radioligand therapy, PARP/HRR-targeted combinations, next-generation AR-pathway agents, and PSMA/PSCA/STEAP1 cell therapies. Trials below are recruiting; phase is noted for each. Confirm current status and eligibility with the study team — a trial's status and locations can change.

PSMA Radioligand Therapy

These require PSMA-positive disease on a PSMA-PET scan. Current trials test radioligands in new combinations and with new isotopes.

NCT05113537 — Abemaciclib (CDK4/6 inhibitor) before 177Lu-PSMA-617 in mCRPC, testing whether it increases PSMA expression and radioligand uptake (Phase 1/2)
NCT05766371 — Pembrolizumab + 177Lu-PSMA-617 in castration-resistant prostate cancer, combining PSMA radioligand therapy with immune-checkpoint blockade (Phase 2)
NCT07259213 — Terbium-161 (161Tb)-RAD402, a next-generation PSMA radioligand using an isotope that also emits short-range electrons, in CRPC (Phase 1/2)

PARP / HRR-Targeted (Biomarker-Selected)

Most relevant if you carry an HRR or BRCA1/2 mutation — ask whether your tumor and blood have been tested.

NCT06582628 — Talazoparib (PARP inhibitor) + enzalutamide after progression on a prior AR-pathway inhibitor, in metastatic prostate cancer (Phase 2)
NCT06844383 — Talazoparib with or without enzalutamide in prostate cancer (Phase 2)

Next-Generation AR-Pathway & Targeted Combinations

New agents paired with an ARSI to overcome or delay AR-pathway resistance.

NCT07244341 — Valemetostat (DS-3201b, EZH1/2 inhibitor) + darolutamide in mCRPC (Phase 1)
NCT06702995 — XNW5004 + enzalutamide in mCRPC (Phase 1/2)
NCT07287150 — Inavolisib (PI3Kα inhibitor) in mCRPC, targeting the PI3K/AKT pathway that cross-talks with AR signaling (Phase 2)
NCT06401980 — Darolutamide in mCRPC (Phase 2)

Cell Therapy & Bispecifics (PSMA / PSCA / STEAP1)

Early-phase trials directing T cells against prostate surface antigens — a frontier for mCRPC, mostly Phase 1.

NCT06236139 — STEAP1-targeted CAR-T cells + enzalutamide in mCRPC (Phase 1/2)
NCT03972657 — REGN5678 (nezastomig, a PSMA×CD28 bispecific), alone or with cemiplimab, in mCRPC (Phase 1/2)
NCT05805371 — PSCA-targeting CAR-T cells, with or without radiation, in PSCA-positive mCRPC (Phase 1)
NCT07543055 — BPX-601, a PSCA-directed CAR-T cell therapy, in prostate cancer (Phase 1)

Chemotherapy & Other Novel Approaches

NCT06470243 — Adding carboplatin to cabazitaxel chemotherapy in mCRPC (Phase 3)
NCT06100705 — Sipuleucel-T immunotherapy combined with bipolar androgen therapy in mCRPC (Phase 2)
NCT06705686 — (R)-9b, a novel ACK1/TNK2 inhibitor, in prostate cancer (Phase 1)

This is a curated snapshot, not the full list. There are 190+ mCRPC trials recruiting (view all on ClinicalTrials.gov), and which ones fit depends on your PSMA-PET status, HRR/BRCA mutations, prior lines of therapy, metastatic sites, and country. Run a personalized match to see the trials you actually qualify for.

Frequently Asked Questions

What does metastatic castration-resistant prostate cancer (mCRPC) mean?

Prostate cancer is castration-resistant when it keeps growing — a rising PSA and/or new or growing metastases — despite hormone therapy (ADT) that has lowered testosterone to castrate levels (below 50 ng/dL). Metastatic means it has spread beyond the prostate, most often to bone and lymph nodes. mCRPC is therefore cancer that is both spread and no longer controlled by testosterone-lowering alone, and it is the setting where the newest PSMA radioligand, PARP, and cell-therapy trials concentrate.

What trials are open for mCRPC?

mCRPC is one of the most active trial settings in oncology. Recruiting examples by mechanism include PSMA radioligand combinations (abemaciclib before 177Lu-PSMA-617, NCT05113537; pembrolizumab + 177Lu-PSMA-617, NCT05766371) and the next-generation radioligand 161Tb-RAD402 (NCT07259213); PARP/HRR combinations (talazoparib + enzalutamide, NCT06582628); next-generation AR-pathway agents (valemetostat + darolutamide, NCT07244341; XNW5004 + enzalutamide, NCT06702995; inavolisib, NCT07287150); and PSMA/PSCA/STEAP1 cell therapies and bispecifics (STEAP1 CAR-T + enzalutamide, NCT06236139; REGN5678 PSMA×CD28 bispecific, NCT03972657; PSCA CAR-T, NCT05805371). Which ones fit you depends on your PSMA-PET status, HRR/BRCA mutations, and prior treatment — paste your summary into ClinTrialFinder for a personalized match.

What is the standard treatment for mCRPC?

ADT continues throughout. On top of it, standard options include androgen-receptor signaling inhibitors (abiraterone, enzalutamide, darolutamide, apalutamide), taxane chemotherapy (docetaxel, then cabazitaxel), 177Lu-PSMA-617 (Pluvicto) for PSMA-positive disease after an ARSI and a taxane, radium-223 for symptomatic bone metastases without visceral disease, sipuleucel-T immunotherapy, PARP inhibitors (olaparib, rucaparib) for HRR/BRCA-mutated tumors, and pembrolizumab for MSI-high/dMMR tumors. Choice depends on symptoms, prior therapy, metastatic sites, and biomarkers. A clinical trial is a reasonable option to consider at any point in this setting.

Why does a PSMA-PET scan matter for trials?

PSMA (prostate-specific membrane antigen) is a protein on most prostate cancer cells. A PSMA-PET scan (using tracers such as 68Ga-PSMA-11 or 18F-piflufolastat) shows whether your tumor is PSMA-positive, which determines eligibility for 177Lu-PSMA-617 (Pluvicto) and for most PSMA radioligand and PSMA-targeted cell-therapy trials. It is the single most important imaging biomarker in mCRPC trial selection.

Do HRR / BRCA mutations change my mCRPC trial options?

Yes. About a quarter of mCRPC tumors carry homologous-recombination-repair (HRR) gene mutations, including BRCA1/2. These predict benefit from PARP inhibitors (olaparib, rucaparib are approved; talazoparib combinations are in trials) and open dedicated biomarker-selected trials. Ask whether you have had germline and tumor (somatic) HRR testing — it is standard to test in mCRPC and it changes which trials you qualify for. MSI-high/dMMR status (rarer) similarly opens immunotherapy options.

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