Pluvicto (Lutetium Lu 177 Vipivotide Tetraxetan / 177Lu-PSMA-617) Clinical Trials (June 2026): 48 Recruiting Interventional Studies in PSMA-Positive mCRPC and Earlier-Disease Settings

Last updated: June 25, 2026

Why Pluvicto Matters — In Plain Language

PSMA (prostate-specific membrane antigen, formal name glutamate carboxypeptidase II / GCPII / FOLH1) is a protein that sits on the surface of prostate cells. Most prostate cancers express PSMA at much higher levels than normal prostate tissue — estimates suggest ~70-80% of prostate cancer cells express PSMA, with the highest expression typically in metastatic castration-resistant prostate cancer (mCRPC). PSMA is also expressed at much lower levels in a small handful of normal tissues: salivary glands, lacrimal glands, kidneys (renal tubules), and small intestine. That biology creates a therapeutic window — a drug that binds PSMA can deliver a payload to cancer cells while only modestly affecting a few normal tissues.

Radioligand therapy is the engineering solution. A radioligand is a two-part molecule: a small-molecule ligand (the "homing missile") that binds a tumor-cell surface marker like PSMA, chemically linked via a chelator to a radioactive isotope (the "payload"). When the ligand binds the cancer cell, the cell pulls the whole molecule inside, and the radioactive isotope delivers radiation from within. Because the isotope used in Pluvicto (lutetium-177) is a beta-emitter with a path length of only about 2 mm in tissue, the radiation is concentrated in the immediate tumor area — it can damage neighboring cancer cells in a small radius, but it does not travel through the body the way external-beam radiation does. The patient becomes selectively radioactive in PSMA-positive areas for a relatively short period (the lutetium-177 half-life is ~6.7 days), then the radioactivity decays.

Pluvicto (177Lu-PSMA-617) was the first PSMA-targeted radioligand therapy to receive FDA approval — it remains the only one approved as of June 2026. Pivotal trials in mCRPC (the VISION trial, FDA March 2022, in patients who had received both an NHA and a taxane; the PSMAfore trial, label expansion 2025, in patients post-NHA but pre-taxane) demonstrated meaningful improvements in radiographic progression-free survival and overall survival vs standard of care.

Because Pluvicto requires PSMA expression on the cancer cells to work, eligibility is established by PSMA-PET imaging upfront. A patient who is being considered for Pluvicto gets a PSMA-PET scan (using 68Ga-PSMA-11 / Locametz or Illuccix, or 18F-DCFPyL / Pylarify / piflufolastat as the imaging tracer) before treatment to confirm that the cancer lesions express enough PSMA for the radioligand to bind. This is a critical eligibility step — without a positive PSMA-PET, treatment is not appropriate, and not all sites have PSMA-PET available locally. Patients should ask their oncologist about PSMA-PET access early in the conversation.

FDA-Approved Indications

Pluvicto has 2 active FDA approvals, both in PSMA-positive metastatic castration-resistant prostate cancer (mCRPC), differing by line of therapy (post-chemotherapy vs pre-chemotherapy).

Active Indications (2)

Pluvicto vs Other mCRPC Treatment Options

Pluvicto is one of several mCRPC treatment options after progression on an NHA. The comparison depends on the patient's specific situation:

• Pluvicto (177Lu-PSMA-617, Novartis) vs cabazitaxel (Jevtana, a taxane chemotherapy): both are options in mCRPC post-NHA and (for the original VISION Pluvicto label) post-docetaxel. Pluvicto requires PSMA-PET-confirmed PSMA-positive disease; cabazitaxel does not require any companion imaging. Toxicity profiles differ: Pluvicto's distinctive on-target effects are xerostomia (dry mouth) and dry eyes, plus cytopenias and radiation safety precautions; cabazitaxel's are severe neutropenia (G-CSF support standard), diarrhea, fatigue, and hypersensitivity reactions. There is an active head-to-head Phase 2: NCT06738303 randomizes cabazitaxel ± carboplatin vs Pluvicto in mCRPC — the first direct prospective comparison. The clinical decision today often comes down to PSMA-PET availability, bone-marrow reserve, and patient preference for radiation-based vs chemotherapy-based treatment.
• Pluvicto vs olaparib (Lynparza, a PARP inhibitor): olaparib is FDA-approved in BRCA / HRR-mutated mCRPC after progression on an NHA (PROfound), and in combination with abiraterone in 1L BRCA-mutated mCRPC (PROpel). The eligibility criterion is fundamentally different — BRCA / HRR mutation status for olaparib vs PSMA-PET status for Pluvicto. Some patients may be eligible for both (BRCA-mutated AND PSMA-positive); the optimal sequence is still being defined, but the typical pattern is to use the BRCA/HRR-targeted option first if mutation-positive, with Pluvicto held for later progression. See the Lynparza drug page for the BRCA / HRR mCRPC discussion.
• Pluvicto vs investigational PSMA radioligands: several next-generation PSMA radioligands are in late-stage development but are not FDA-approved as of June 2026. The most advanced is AAA817 (225Ac-PSMA-617, Novartis), the actinium-225 alpha-emitter successor using the same PSMA-617 chelator backbone as Pluvicto — NCT06780670 is the registrational Phase 2/3 in patients whose disease progressed on or after 177Lu-PSMA (the most clinically-pressing post-Pluvicto sequencing question). Other investigational agents: AZD2265 / FPI-2265 (AstraZeneca / Fusion) 225Ac with the PSMA-I&T chelator (Phase 3 VECTRA-01); 177Lu-TLX591 (Telix Pharmaceuticals) antibody-based 177Lu PSMA (Phase 3 ProstACT Global, NCT06520345); terbium-161 (161Tb) PSMA Auger-electron agents in earlier development; 177Lu-PSMA-I&T with an alternative chelation chemistry; and 225Ac-J591 antibody-based alpha-emitter. See the PSMA Radioligand Therapy mechanism hub for the cross-drug comparison.
• Pluvicto vs bispecific T-cell engagers (xaluritamig, pasritamig): bispecific T-cell engagers (BiTEs) that direct T cells to STEAP1 (xaluritamig) or PSMA (pasritamig) on prostate cancer cells are reaching Phase 3 in mCRPC (NCT07213674 xaluritamig + abiraterone in chemo-naive mCRPC; NCT07164443 pasritamig in late-line mCRPC). These are entirely different mechanisms from radioligand therapy — immune-mediated killing rather than radiation. Toxicity profile differs sharply (cytokine release syndrome / immune effector cell-associated neurotoxicity for BiTEs vs xerostomia / cytopenias for Pluvicto). None are FDA-approved as of June 2026.
• Frame fairly: ask your oncologist about all of the options that apply to your situation. Sequencing across mCRPC therapy classes (radioligand, chemotherapy, PARP inhibitor, bispecific) is an active area of research — the optimal order is patient-specific.

PSMA-PET Diagnostic Pathway — Companion Imaging for Pluvicto Eligibility

Because Pluvicto eligibility depends on PSMA expression, a PSMA-PET scan upfront is a non-negotiable step in the workflow. Two FDA-approved PSMA-PET tracer families are commonly used:

• 68Ga-PSMA-11 PET — gallium-68 labeled PSMA-11. FDA-approved tracers in this family: Locametz (Novartis, the diagnostic kit paired with Pluvicto) and Illuccix (Telix Pharmaceuticals). Gallium-68 is a positron emitter with a short half-life (~68 minutes) and requires on-site or near-site cyclotron / generator availability.
• 18F-DCFPyL / piflufolastat PSMA PET — fluorine-18 labeled DCFPyL. FDA-approved tracer: Pylarify (Lantheus). Fluorine-18 has a longer half-life (~110 minutes), which enables broader distribution from regional cyclotron sites to community PET imaging centers.
• Eligibility threshold: the scan must demonstrate sufficient PSMA expression on the patient's tumor lesions for the radioligand to bind in therapeutically meaningful amounts. The exact reading criteria are described in the FDA label and in the clinical-trial protocols (the VISION trial defined PSMA-positive based on a defined SUV threshold relative to liver background). The reading is performed by a trained nuclear medicine physician.
• Counter-screening for PSMA-low or PSMA-negative disease: a meaningful subset of mCRPC patients (estimates roughly 10-30% depending on series and reading cutoff) have PSMA-low or PSMA-negative disease and do not qualify for the standard Pluvicto label. These patients have a distinct trial pathway: NCT06526299 (LPS-Boost, intensified 177Lu-PSMA-617 dosing for PSMA-low mCRPC) and NCT06145633 (vorinostat HDAC priming to upregulate PSMA expression before / during 177Lu-PSMA-617). PSMA-low patients should ask their oncologist about these trial pathways and about alternative mCRPC options (cabazitaxel chemotherapy, BRCA / HRR-targeted PARP inhibitors if mutation-positive, bispecific T-cell engagers in trials).

Recruiting Pluvicto Trials

Curated subset of recruiting interventional Pluvicto (177Lu-PSMA-617) trials in the ClinTrialFinder corpus as of June 25, 2026 (approximately 48 recruiting + not-yet-recruiting trials total). Trials are grouped by clinical setting and ordered by phase and significance. Some trials also test next-generation PSMA radioligand agents (AAA817 / 225Ac-PSMA-617, 177Lu-TLX591) for sequencing and cross-agent comparison.

Phase 3 — Registrational Programs and Earlier-Disease Expansion

• NCT06496581 — Phase 3 (PEACE6 Poor-Responders): SOC ± 177Lu-PSMA-617 in de novo mHSPC patients with poor PSA response to first-line ADT + ARPI. Brings Pluvicto into the hormone-sensitive setting — far earlier than the current mCRPC label — for patients with biologic / clinical aggressiveness signals. Status: Recruiting.
• NCT05939414 — Phase 3: 177Lu-Vipivotide vs Observation in PSMA-Positive Oligometastatic Prostate Cancer. Tests Pluvicto as a potential curative-intent option in low-disease-burden oligometastatic patients — far earlier than the current label. Status: Recruiting.
• NCT06520345 — Phase 3 (ProstACT Global): 177Lu-TLX591 (Telix's antibody-based 177Lu PSMA radioligand) + SOC vs SOC alone in mCRPC. Tests a next-generation PSMA-class agent against SOC; not Pluvicto, but informs the PSMA radioligand class. Status: Recruiting.
• NCT07200830 — Phase 3 (RECIPROCAL, NCI): Tests different dosing schedules of Pluvicto (177Lu-PSMA-617) and their effect on patients with advanced prostate cancer. NCI-led schedule-optimization trial — could refine the standard 6-cycle every-6-weeks regimen. Status: Recruiting.

Phase 2/3 + Phase 4 — Next-Generation Programs and Longitudinal Safety

• NCT06780670 — Phase 2/3: AAA817 (225Ac-PSMA-617, the Novartis actinium-225 alpha-emitter successor to Pluvicto) vs SOC in previously treated PSMA-positive mCRPC after 177Lu-PSMA-targeted therapy. The most clinically-pressing post-Pluvicto sequencing question — does the alpha-emitter work after the beta-emitter fails? Status: Recruiting.
• NCT05803941 — Phase 4: Long-Term Safety of 177Lu-PSMA-617 in mCRPC. Novartis-sponsored extension capturing late-emerging safety signals (secondary myelodysplasia / AML, persistent xerostomia, renal function over time). Status: Recruiting.
• NCT06099093 — Phase 4 (Imaging-Guided Pluvicto): PSMA-PET-imaging-guided 177Lu-PSMA-617 in mCRPC — tests whether PSMA-PET-driven dose / cycle decisions improve outcomes over fixed-schedule dosing. Status: Recruiting.

Phase 2 — mCRPC Treatment Optimization (Re-Treatment, Schedule, Dosing)

• NCT06866938 — Phase 2: Re-Treatment with Pluvicto in mCRPC Patients Who Previously Progressed on 177Lu-PSMA-617. Tests whether a second course of Pluvicto can produce response in patients who initially responded and later progressed. Status: Recruiting.
• NCT06288113 — Phase 2 (RE-LuPSMA): Re-Treatment with 177Lu-PSMA-617 in mCRPC. Companion re-treatment trial. Status: Recruiting.
• NCT06200103 — Phase 2: Schedule De-Escalation of 177Lu-PSMA-617 in mCRPC. Tests whether fewer or longer-interval cycles can preserve efficacy while reducing cumulative radiation exposure. Status: Recruiting.
• NCT06216249 — Phase 2 (FLEX-MRT): Flexible Dosing Schedule of 177Lu-PSMA-617 in mCRPC. Personalizes dosing based on tumor response, imaging, and tolerability. Status: Recruiting.
• NCT06738303 — Phase 2 (Head-to-Head): Cabazitaxel ± Carboplatin vs 177Lu-PSMA-617 in mCRPC. The first direct prospective head-to-head comparison of Pluvicto vs the standard post-docetaxel chemotherapy comparator — a major question for sequencing in PSMA-positive mCRPC patients eligible for both. Status: Recruiting.

Phase 2 — Combinations and Earlier-Line Settings

• NCT05766371 — Phase 2: Pembrolizumab + 177Lu-PSMA-617 in mCRPC. Tests whether PD-1 checkpoint inhibition synergizes with PSMA radioligand therapy — prostate cancer has historically been minimally responsive to checkpoint monotherapy. Status: Recruiting.
• NCT05893381 — Phase 2: 177Lu-PSMA-617 + SBRT vs SBRT Alone in Oligometastatic Prostate Cancer. Tests whether adding Pluvicto to stereotactic body radiotherapy improves outcomes in low-burden disease. Status: Recruiting.
• NCT05560659 — Phase 2: Lu-PSMA + SABR (Stereotactic Ablative Radiotherapy) for Oligometastatic Prostate Cancer. Companion oligometastatic combination strategy. Status: Recruiting.
• NCT06449781 — Phase 2: Pluvicto as Adjuvant Therapy in Very-High-Risk Localized Prostate Cancer. Tests the radioligand class in the curative-intent localized setting — a paradigm shift from the metastatic label. Status: Recruiting.
• NCT05113537 — Phase 1/2: Abemaciclib Before 177Lu-PSMA-617 in mCRPC. Tests CDK4/6 inhibitor priming to sensitize cancer cells to subsequent PSMA radioligand therapy. Status: Recruiting.

Phase 2 — Low-PSMA-Expressing Disease (PSMA-Boost Strategies)

Patients with PSMA-low imaging are typically excluded from the standard Pluvicto label. These two trials specifically enroll PSMA-low patients with strategies to extend radioligand benefit.

• NCT06526299 — Phase 2 (LPS-Boost): Intensified 177Lu-PSMA-617 Treatment in Patients with Low-PSMA-Expressing mCRPC. Higher / intensified dosing strategy to deliver therapeutic radiation despite lower target density. Status: Recruiting.
• NCT06145633 — Phase 2: Vorinostat + 177Lu-PSMA-617 in PSMA-Low mCRPC. HDAC inhibitor to upregulate PSMA expression on prostate cancer cells before / during Pluvicto — converting PSMA-low disease into a PSMA-treatable target. Status: Recruiting.

Cross-Cancer Signals + Novel Chemistry (Alpha vs Beta, Combinations)

Pluvicto is being studied beyond prostate cancer (cross-cancer PSMA expression on tumor neovasculature) and in next-generation chemistry comparisons (alpha-emitters, alternative chelators, immune combinations). None of these are FDA-approved indications or combinations.

• NCT07223034 — Phase 1 (Cross-Cancer): Pluvicto in Gliomas. PSMA expression on tumor neovasculature provides a different rationale than the prostate-cancer label — a signal-finding cross-cancer study. Status: Recruiting.
• NCT07054346 — Phase 1 (Head-to-Head Isotope): 177Lu-PSMA-617 vs 225Ac-PSMA-617 in mCRPC. Direct comparison of the beta-emitter (lutetium-177) and alpha-emitter (actinium-225) using the same PSMA-617 chelator backbone. Status: Recruiting.
• NCT04886986 — Phase 1/2 (Alpha+Beta Combo): 225Ac-J591 + 177Lu-PSMA-617 in mCRPC. Combination of an antibody-based alpha-emitter (225Ac-J591) with the small-molecule beta-emitter Pluvicto — tests whether dual-modality radiation overcomes resistance to either alone. Status: Recruiting.
• NCT07219147 — Phase 1/2 (Immune Combo): Pluvicto + Sipuleucel-T in mCRPC. Tests autologous prostate cancer immunotherapy (sipuleucel-T / Provenge) combined with PSMA radioligand therapy — PSMA-radiation-induced immunogenic cell death may synergize with the vaccine. Status: Recruiting.
• NCT07090369 — Phase 1b (Novel-Radioligand Combo): 177Lu-PSMA-I&T + Olaparib + Pembrolizumab. Tests a different 177Lu PSMA chelator (PSMA-I&T rather than PSMA-617) in combination with a PARP inhibitor (olaparib) and PD-1 checkpoint inhibitor (pembrolizumab) — multi-modality strategy for late-line PSMA-positive mCRPC. Status: Recruiting.

Showing a curated subset of recruiting Pluvicto (177Lu-PSMA-617) interventional trials in the ClinTrialFinder corpus as of June 25, 2026 (approximately 48 recruiting + not-yet-recruiting trials total). For the latest list: view all recruiting 177Lu-PSMA-617 trials on ClinicalTrials.gov.

Mechanism: PSMA-Targeted Radioligand With Lutetium-177 Beta-Emitter Payload

Side Effects and Practical Considerations

Bone Marrow Suppression (Cytopenias)

Beta radiation from lutetium-177 also reaches the bone marrow, causing dose-dependent suppression of red cells (anemia), platelets (thrombocytopenia), and white cells (neutropenia). Routine CBC monitoring is part of every cycle; cytopenias can be dose-limiting and may require cycle delays, dose reduction, or supportive transfusions / G-CSF. Patients with significant pre-existing cytopenias or extensive prior cytotoxic exposure may have less marrow reserve to tolerate the full 6-cycle course.

Renal Function

PSMA is also expressed on the renal tubules, so the kidneys receive some on-target radiation, and the radiolabeled ligand is cleared through the kidneys. Renal function monitoring (creatinine, eGFR) is routine before and during treatment. Patients should maintain good hydration. The radioactive material is excreted primarily in urine for the first ~24-48 hours after each infusion.

Other Common Adverse Events

• Nausea, vomiting — common but typically manageable with standard antiemetic premedication.
• Fatigue — commonly reported, typically mild to moderate.
• Decreased appetite, constipation — commonly reported.
• Dry eyes — on-target lacrimal gland radiation; supportive lubricating eye drops as needed.

Radiation Safety Precautions

Pluvicto delivers radioactivity to the patient's body. For approximately 24-48 hours after each infusion, the patient excretes radioactive material primarily in urine. Lower-level radioactivity persists for approximately 1-2 weeks (driven by the ~6.7 day lutetium-177 half-life). The radiation oncology and nuclear medicine team will provide radiation safety counseling covering:

• Distance from infants, young children, and pregnant partners — maintain distance and limit prolonged close contact for the first 1-2 weeks (the higher-excretion / higher-radiation period).
• Toilet hygiene — flush the toilet twice, wash hands thoroughly, and avoid splash. Men should sit to urinate during the high-excretion period.
• Sleeping arrangements — some sites recommend separate sleeping arrangements from infants / pregnant partners for the first few nights.
• Contraception — recommendations are provided by the treating team; verify the latest FDA label.
• Travel — the patient may set off radiation detectors at airports and border crossings for several days to weeks after each infusion; the treating team can provide a treatment card / documentation.

Long-Term: Secondary Myelodysplasia / AML

Secondary myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML) are rare but documented in long-term follow-up of patients treated with radioligand therapies, particularly in patients with extensive prior cytotoxic chemotherapy exposure or significant prior radiation. This is a recognized late-effect concern of any cytotoxic / radiation-based therapy that reaches the bone marrow. The absolute risk over the typical Pluvicto treatment course appears low based on available data, but long-term Phase 4 surveillance (NCT05803941 long-term safety extension) continues to characterize this signal. The risk-benefit conversation is part of the informed-consent discussion before treatment.

Frequently Asked Questions