Until very recently, prostate cancer Phase 3 trials were dominated by variations on the same three pillars: androgen deprivation therapy (ADT), AR-pathway inhibitors (ARPIs like enzalutamide, apalutamide, darolutamide, abiraterone), and chemotherapy (docetaxel, cabazitaxel). The 2022 FDA approval of lutetium-177-PSMA-617 (Pluvicto) for previously-treated metastatic castration-resistant prostate cancer (mCRPC) — expanded in 2025 to the pre-chemotherapy mCRPC setting — cracked open a new modality: targeted radionuclide therapy. ASCO 2026 is the conference where the next wave of mechanisms reaches Phase 3 visibility.
Four trends define the 2026 landscape:
Here's what to watch at ASCO 2026.
NCT05939414 (Novartis) is a Phase 3 testing 177Lu-PSMA-617 (Pluvicto) versus observation in patients with biochemically recurrent (BCR) prostate cancer who have oligometastatic recurrence after definitive primary treatment (radical prostatectomy or external beam radiotherapy). The trial's primary aim is to delay the start of androgen deprivation therapy (ADT) by treating the oligometastatic disease with PSMA-targeted radioligand therapy — preserving quality of life from ADT side effects. This pushes Pluvicto upstream from its current FDA-approved label (previously-treated mCRPC) into a much earlier disease setting where it competes with metastasis-directed radiotherapy.
NCT06855277 (Novartis) is a 3-arm Phase 3 in PSMA-positive mCRPC patients who have already received an ARPI: AAA817 (actinium-225-PSMA-617, an alpha-emitter radioligand) + ARPI vs AAA817 monotherapy vs investigator's choice standard of care (ARPI change OR taxane chemo OR 177Lu-PSMA-617 itself). The key distinction from Pluvicto is the radiation type: lutetium-177 (Pluvicto) emits beta particles with longer range, while actinium-225 emits alpha particles with very short range (~50-100 micrometers, 2-10 cell diameters) and much higher linear energy transfer — concentrated cytotoxicity per decay. Because the SoC control arm includes 177Lu-PSMA-617 as one option, the trial is effectively a partial head-to-head of alpha-emitter actinium vs beta-emitter lutetium PSMA-targeted therapy.
NCT06780670 (Novartis) is a combined Phase 2/3 of AAA817 (actinium-225-PSMA-617) specifically in patients with PSMA-positive mCRPC who have progressed on or after 177Lu-PSMA-617 (Pluvicto) — i.e., the tail end of the current PSMA-targeted therapy sequence. Phase 2 portion does dose-finding (AAA817 Dose A vs Dose B); Phase 3 portion compares the recommended dose against investigator's choice of standard of care. Together with AcTFirst, the AAA817 program tests both earlier-line (post-ARPI) and later-line (post-Pluvicto) settings for the alpha-emitter.
NCT06520345 (Telix Pharmaceuticals), known as ProstACT Global, tests lutetium (177Lu) rosopatamab tetraxetan (177Lu-TLX591) + standard-of-care (enzalutamide or abiraterone or docetaxel) versus standard of care alone in mCRPC patients who have progressed on ARPI. Rosopatamab is a monoclonal antibody targeting PSMA — a different molecular format from Novartis's small-molecule vipivotide tetraxetan (Pluvicto). The two formats may produce different toxicity and efficacy profiles (antibody-based PSMA radioligands typically have longer circulation times and different tumor penetration), opening choice for patients.
NCT06496581 (UNICANCER), known as PEACE6-Poor Responders, tests adding 177Lu-PSMA-617 to standard of care in patients with de novo metastatic hormone-sensitive prostate cancer (mHSPC) who have a PSA ≥0.2 ng/mL at 6-8 months after starting standard of care (i.e., have an inadequate PSA response). This moves PSMA radioligand therapy into the first-line metastatic setting specifically for patients whose ADT response is suboptimal — a clinically high-need group where intensification options are limited.
NCT06320067 is the UK's STAMPEDE2 — a randomized controlled platform trial in metastatic hormone-sensitive prostate cancer testing multiple treatments simultaneously, including both SABR (stereotactic ablative radiotherapy) comparisons and a 177Lu-PSMA-617 comparison. Platform trials like STAMPEDE/STAMPEDE2 have a strong track record in prostate cancer for establishing new standards of care.
NCT06764485 (Celgene / Bristol Myers Squibb) tests BMS-986365 versus investigator's choice of therapy (a second ARPI OR docetaxel) in mCRPC patients who have previously received an ARPI. The trial is a 2-part adaptive Phase 3 (Part 1 dose selection comparing two BMS-986365 doses; Part 2 main efficacy comparison at the selected dose). BMS-986365 is an investigational AR-targeted agent that published literature has described as an AR ligand-directed degrader (a class that targets the AR protein for proteasomal degradation, rather than blocking AR signaling like the existing ARPIs do); the trial registration itself does not describe the mechanism class. Confirm the specific mechanism with your oncologist before considering this trial.
NCT06136624 (Merck) tests opevesostat (MK-5684), a CYP11A1 inhibitor, versus alternative next-generation hormonal agents (abiraterone or enzalutamide) in mCRPC. CYP11A1 is the rate-limiting enzyme in the steroidogenesis pathway; inhibiting it cuts off both gonadal AND adrenal androgen synthesis at the source. (A companion trial, NCT06136650, tests opevesostat with hormone-replacement-therapy add-back to manage the adrenal-insufficiency side effects.)
NCT07260435 tests ADT + only 12 months of ARPI (apalutamide or enzalutamide) — with the possibility to restart treatment if disease progresses — vs ADT + continued ARPI, specifically in low-volume mCSPC (high-volume patients excluded). The intermittent design tests whether discontinuation after 12 months, with reintroduction on progression, is non-inferior to continuous ARPI. This addresses one of the most patient-relevant questions in modern prostate care for the low-volume metastatic group: do you really need indefinite ARPI, or is 12 months with on-demand restart enough? Long-term ARPI has significant side effects (fatigue, cardiovascular, metabolic, cognitive) that compound over years — if intermittent dosing delivers equivalent outcomes, the quality-of-life upside is substantial.
NCT06120491 (AstraZeneca) tests saruparib (AZD5305, a PARP1-selective inhibitor) + physician's choice of next-generation hormonal agent vs placebo + NHA in metastatic castration-sensitive prostate cancer (mCSPC) — and notably enrolls both HRR-mutated (HRRm) and non-HRR-mutated patients. Until now, PARP inhibitors in prostate (olaparib, talazoparib, rucaparib, niraparib) have been used primarily in mCRPC, often after ARPI failure and typically in HRR-mutated patients. Moving saruparib into mCSPC AND testing in non-HRRm patients (where PARP inhibitor benefit has historically been less clear) is a significant expansion of the PARP indication.
NCT06952803 (AstraZeneca) is a Phase 3 testing saruparib added to standard radiotherapy + ADT in patients with BRCA1- or BRCA2-mutated localised/locally advanced high-risk (or very-high-risk) prostate cancer. Enrollment requires a confirmed BRCA1 or BRCA2 mutation. The trial has 2 cohorts (Cohort A: saruparib or placebo + ADT; Cohort B: saruparib or placebo + ADT + abiraterone), and uses metastases-free survival (MFS) as the primary endpoint. Notably, this is BRCA-required only (no broader HRR enrollment) and addresses the localised high-risk setting — earlier in disease course than mCSPC. Together, EvoPAR-PR01 (mCSPC, HRRm + non-HRRm) and EvoPAR-PR02 (localised high-risk, BRCAm only) represent AstraZeneca's bet that saruparib's PARP1-selective profile (vs the older non-selective PARP1/2 inhibitors) may produce a better tolerability/efficacy balance.
NCT06439225 (Canadian Cancer Trials Group) tests carboplatin + docetaxel vs docetaxel alone in mCRPC patients with DNA damage repair (DDR) alterations (including BRCA1/2, ATM, and other HRR genes). The hypothesis: DDR-deficient tumors are platinum-sensitive, so adding platinum to standard taxane chemo should improve outcomes specifically for this molecularly-selected subgroup.
NCT07164443 (Janssen) tests pasritamig — a bispecific T-cell engager targeting kallikrein-2 (KLK2, a prostate-tissue-specific protein) — vs placebo, both added to best supportive care, in late-line mCRPC. T-cell engagers have been extraordinarily successful in hematologic cancers (teclistamab in myeloma, blinatumomab in ALL, etc.) but the solid-tumor T-cell engager story has been slower. KLK2 is highly prostate-specific, which may overcome the off-target toxicity that has limited solid-tumor T-cell engagers so far. Pasritamig is one of the first prostate-targeted T-cell engagers to reach a registrational Phase 3.
NCT04916613 (UNICANCER), also known as PEACE6-Vulnerable, tests ADT + darolutamide vs ADT + placebo in castration-naïve de novo metastatic prostate cancer patients with vulnerable functional ability who have NOT elected for docetaxel or other ARPIs (i.e., patients who declined intensification due to vulnerability/frailty). Most ARPI registration trials enroll fit patients (ECOG 0-1); this trial specifically asks whether vulnerable patients — typically excluded from registration trials — also benefit from ARPI intensification on top of ADT.
NCT06592924 (Canadian Cancer Trials Group) tests ADT + ARPI + docetaxel vs ADT + ARPI alone in mCSPC patients who have had a suboptimal PSA response after 6-12 months on the doublet. Critically, this is NOT a de novo triplet trial — patients enter the study after their ADT+ARPI response has plateaued or proved insufficient, and the trial asks whether ADDING docetaxel at that point salvages outcomes. This is a different question than the de novo triplet trials (PEACE-1, ARASENS) that established the triplet as initial therapy for high-volume mCSPC. TRIPLE-SWITCH addresses the practical clinical question: if your ADT + ARPI isn't working as expected, is delayed docetaxel still worthwhile?
NCT06625970 (UNICANCER) is a Phase 3 with a 2x2 factorial design (4 arms): standard ADT + conventional radiotherapy, vs that + darolutamide, vs that + SBRT, vs that + both darolutamide and SBRT. Patients must meet at least 2 NCCN high-risk criteria. The factorial design lets the trial answer two independent questions in one study: (a) does adding darolutamide to ADT + RT improve outcomes? (b) does SBRT improve on conventional radiotherapy in this setting? SBRT (5-fraction radiation) has been steadily replacing conventional multi-week radiation in prostate cancer; PEACE 7 evaluates both that question and the ARPI-intensification question simultaneously.
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Find Matching TrialsThis page is for information only and is not medical advice. ClinTrialFinder helps you find clinical trials that may match your situation, but enrollment decisions and treatment choices should always be made with your oncologist or healthcare team. Trial eligibility, recruitment status, and treatment details can change — verify directly with the trial sponsor or on ClinicalTrials.gov before acting on any information here. ASCO 2026 may surface additional data not yet reflected on this page; check the trial registry for the most current status.