Clinical trials

Pluvicto®▼(lutetium [ 177Lu] vipivotide tetraxetan) is indicated for the treatment of adult patients with:1

  • Prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have progressed on or after treatment with androgen receptor pathway inhibitor (ARPI) therapy and are considered appropriate to delay taxane-based chemotherapy
    PSMA-positive mCRPC who have been treated with androgen receptor (AR) pathway inhibition and taxane-based chemotherapy or who are not medically suitable for taxanes

Pluvicto Summary of Product Characteristics (SmPC) can be found here.

Locametz®▼(gozetotide) is for diagnostic use only. Locametz, after radiolabelling with gallium-68, is a radioactive diagnostic agent indicated for the identification of PSMA-positive lesions by positron emission tomography (PET) in adult patients with prostate cancer.2

The data from the PSMAfore and VISION trials cannot be extrapolated to any other lutetium PSMA therapy.

  • PSMAfore clinical trial
  • PSMAfore efficacy
  • PSMAfore QoL
  • PSMAfore PSA

    PSMAfore was a Phase III, randomised, controlled trial conducted at 74 sites across Europe and North America (n=468), investigating the efficacy of Pluvicto compared with a change of ARPI (to either abiraterone or enzalutamide) in taxane-naïve patients with PSMA-positive mCRPC who had progressed once on a previous ARPI. The primary endpoint was radiographic progression-free survival (rPFS). The key secondary endpoint was overall survival (OS).3

     

    PSMAfore study design:

    pluvicto-clinical-trials-PSMAfore-tab1-graph1

    PSMAfore primary and secondary endpoints:

    pluvicto-clinical-trials-PSMAfore-tab1-graph2

    PSMAfore exclusion criteria:³

    1. Previous treatment with any of the following within 6 months of randomisation: Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, Radium-223, hemi-body irradiation

    2. Previous PSMA-targeted RLT therapy

    3. Prior treatment with cytotoxic chemotherapy for castration resistant or castrate sensitive prostate cancer (e.g., taxanes, platinum, estramustine, vincristine, methotrexate, etc.), immunotherapy or biological therapy [including monoclonal antibodies]. [Note: taxane exposure (maximum 6 cycles) in the adjuvant or neoadjuvant setting was allowed if 12 months had elapsed since completion of this adjuvant or neoadjuvant therapy. Prior treatment with sipuleucel-T was allowed]

    4. Any investigational agents within 28 days prior to day of randomisation

    5. Known hypersensitivity to any of the study treatments or its excipients or to drugs of similar classes

    6. Concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy, PARP inhibitor, biological, or investigational therapy

    7. Transfusion or use of bone marrow stimulating agents for the sole purpose of making a participant eligible for study inclusion

    8. Participants with a history of CNS metastases who are neurologically unstable, symptomatic, or receiving corticosteroids for the purpose of maintaining neurologic integrity. Participants with CNS metastases were eligible if received therapy (surgery, radiotherapy, gamma knife), asymptomatic and neurologically stable without corticosteroids. Participants with epidural disease, canal disease and prior cord involvement were eligible if those areas had been treated, were stable, and not neurologically impaired

    9. Symptomatic cord compression, or clinical or radiologic findings indicative of impending cord compression

    10. History or current diagnosis of the following ECG abnormalities indicating significant risk of safety for study participants:

    • Concomitant clinically significant cardiac arrhythmias, e.g. sustained ventricular tachycardia, complete left bundle branch block, high-grade AV block (e.g., bifascicular block, Mobitz type II and third degree AV block)

    • History of familial long QT syndrome or known family history of Torsades de Pointe

    • Cardiac or cardiac repolarisation abnormality, including any of the following: history of MI, angina pectoris, or CABG within 6 months prior to starting study treatment

    1. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, known active hepatitis B or C or other significant comorbid conditions that in the opinion of the investigator would impair study participation or cooperation

    • HIV-infected participants who were at a low risk of AIDS-related outcomes could participate in this trial

    • Participants with an active documented COVID-19 infection (any grade of disease severity) at time of informed consent could be included only when completely recovered (in accordance with local guidance)

    1. Diagnosed with other malignancies that were expected to alter life expectancy or could interfere with disease assessment. Participants with a prior history of malignancy that had been adequately treated and who had been disease free and treatment free for more than 3 years prior to randomisation were eligible, as were participants with adequately treated non-melanoma skin cancer and superficial bladder cancer

    2. Sexually active males unwilling to use a condom during intercourse while taking study treatment and for 14 weeks after stopping study treatment. A condom was required for all sexually active male participants to prevent them from fathering a child AND to prevent delivery of study treatment via seminal fluid to their partner. In addition, male participants could not donate sperm for the time period specified above. If local regulations deviated from the contraception methods listed above to prevent pregnancy, local regulations applied

    3. Unmanageable concurrent bladder outflow obstruction or urinary incontinence. Note: participants with bladder outflow obstruction or urinary incontinence, which was manageable and controlled with BSoC (including pads, drainage) were allowed

    4. History of somatic or psychiatric disease/condition that could interfere with the objectives and assessments of the study

    5. Any condition that precluded raised arms position

    6. Eligible for treatments other than ARDT based on presence of any mutations or biomarkers that are known as predictors of better response (e.g., AR-V7 or BRCA)

    7. Not able to understand and to comply with study instructions and requirements

    *Six or fewer cycles of adjuvent chemotherapy ≥12 months ago was allowed.3
    †PSMA-positive metastatic lesion defined as ⁶⁸Ga-PSMA-11 uptake greater than in liver parenchyma. All lymph nodes measuring 25 mm or greater in the short axis, bone metastases with a soft tissue component 10 mm or greater in the longest diameter, solid organ metastases 10 mm or greater in the longest diameter, and all intraprostatic lesions had to be PSMA-positive on ⁶⁸Ga-PSMA-11 PET-CT.3
    ‡Following one instance of disease progression on abiraterone, enzalutamide, darolutamide or apalutamide as their most recent systematic anticancer therapy.3
    §Assessed by blinded independent central review per Prostate Cancer Working Group (PCWG) 3-modified RECIST v1.1.3
    Third data cutoff refers to the third interim OS analyses that were planned to occur at approximately 223 deaths.3
    ‖PFS was based on radiographic, clinical or PSA progression. PSA response was defined as a ≥50% decrease in PSA concentration from baseline. Second-PFS was based on investigator-assessed radiographic, clinical or PSA progression on a subsequent line of therapy, including crossover therapy.3 
    **Time to PSA progression was based on an increase of ≥25% and ≥2 ng/mL from nadir or from baseline beyond 12 weeks.3

    ‘Chemotherapy’ denotes taxane-based regimens unless otherwise specified.

    pluvicto-clinical-trials-PSMAfore-tab2-graph1.png
    pluvicto-clinical-trials-PSMAfore-tab2-graph2.png
    pluvicto-clinical-trials-PSMAfore-tab2-graph3.png

    *Data are from the primary analysis of the primary endpoint. At data-cut off, one patient had not yet been randomised and was subsequently randomised to the Pluvicto group.3
    †Median rPFS had matured by the third data cutoff, demonstrating a clinically meaningful difference between the two arms.3
    ‡The median time from randomisation to third data cutoff was 24.11 months (20.24–27.40). At the third data cutoff, 134 (57%) of 234 patients allocated to the ARPI change group had crossed over to receive Pluvicto, representing 78% of patients who had radiographic progression confirmed by blinded independent central review.3
    §Third data cutoff refers to the third interim OS analyses that were planned to occur at approximately 223 deaths.3
    At the time of the final OS analysis, 299 deaths were reported in 142/234 participants (60.7%) in the Pluvicto arm and 157/234 (67.1%) in the ARPI change arm; deaths were related to prostate cancer in 115/142 (81.0%) and 130/157 (82.8%), respectively. Among the participants who crossed over, 90/141 (63.8%) died; 79/90 (87.8%) deaths were related to prostate cancer.4

    pluvicto-clinical-trials-PSMAfore-tab3-slide1

    FACT-P is the prostate cancer subscale of FACT, which is specifically designed to measure prostate-cancer-specific QoL. The total score is the sum of the scores of 39 items of the questionnaire and ranges from 1–156, with higher scores indicating better QoL. Assessments may be either self-completed by the subject or administered via face-to-face interviews and completed by a caretake or clinician.3

    pluvicto-clinical-trials-PSMAfore-tab3-slide2.png
    pluvicto-clinical-trials-PSMAfore-tab3-slide3.png

    BPI-SF is used to assess the severity of pain and its impact on daily functions. Scores range from 0–10, with lower scores representing lower levels of pain intensity. Assessments may be either self-completed by the subject or administered via face-to-face interview and completed by a caretaker/clinician.3

    *Time to worsening of FACT-P total score; events were a decrease of ≥10 points, clinical disease progression or death.3,4
    †Third data cutoff refers to the third interim OS analyses that were planned to occur at approximately 223 deaths.3
    ‡Death without an SSE.3
    §Stratified Cox proportional-hazards model.3
    Time to worsening on the BPI-SF pain intensity scale was assessed as the time to a ≥2-point or ≥30% increase from baseline, clinical disease progression, or death.3

    pluvicto-clinical-trials-PSMAfore-tab4-slide1.png
    pluvicto-clinical-trials-PSMAfore-tab4-slide2.png

    *PSA progression was defined as the time from randomisation to the following: ≥25% increase and ≥2 ng/mL above the nadir, confirmed by second value ≥3 weeks later if there was decline from baseline; or ≥25% increase and ≥2 ng/mL increase from baseline beyond 12 weeks if there was no decline from baseline. Assessments were at 3, 6 and 12 months after randomisation.3
    †Increases greater than 100% are truncated to 100%. Assessments were at 3, 6 and 12 months after randomisation.3

  • VISION clinical trial
  • VISION efficacy
  • VISION QoL
  • VISION PSA

    VISION was an international, prospective, randomised, open-label, multicentre, Phase III study (N=831) to assess the efficacy and safety profile of Pluvicto plus investigator-chosen best standard of care (BSoC) in the investigational arm, versus BSoC in the control arm. Patients with PSMA PET-scan positive mCRPC, and progression after prior taxane and AR pathway inhibitors, were randomised in a 2:1 ratio in favour of the investigational arm. The alternate primary endpoints were rPFS and OS.5

     

    VISION study design including primary and secondary endpoints:

    pluvicto-clinical-trials-vision-tab1-graph1.png

    VISION exclusion criteria:⁵

    1. Previous treatment with Strontium-89, Samarium-153, Rhenium-186, Rhenium-188, 223Ra or hemi-body irradiation within 6 months prior to randomisation. Previous PSMA-targeted RLT is not allowed

    2. Any systemic anti-cancer therapy (e.g. chemotherapy, immunotherapy or biological therapy [including monoclonal antibodies]) within 28 days prior to day of randomisation

    3. Any investigational agents within 28 days prior to day of randomisation

    4. Known hypersensitivity to the components of the study therapy or its analogues

    5. Other concurrent cytotoxic chemotherapy, immunotherapy, radioligand therapy or investigational therapy

    6. Transfusion for the sole purpose of making a subject eligible for study inclusion

    7. Patients with a history of central nervous system (CNS) metastases must have received therapy (surgery, radiotherapy, gamma knife) and be neurologically stable, asymptomatic and not receiving corticosteroids for the purposes of maintaining neurological integrity. Patients with epidural disease, canal disease and prior cord involvement are eligible if those areas have been treated, are stable and not neurologically impaired. For patients with parenchymal CNS metastasis (or a history of CNS metastasis), baseline and subsequent radiological imaging must include evaluation of the brain (MRI preferred or CT with contrast)

    8. A superscan as seen in the baseline bone scan

    9. Symptomatic cord compression or clinical or radiological findings indicative of impending cord compression

    10. Concurrent serious (as determined by the Principal Investigator) medical conditions, including, but not limited to, New York Heart Association class III or IV congestive heart failure, history of congenital prolonged QT syndrome, uncontrolled infection, active hepatitis B or C or other significant co-morbid conditions that in the opinion of the investigator would impair study participation or cooperation

    11. Diagnosed with other malignancies that are expected to alter life expectancy or may interfere with disease assessment. Patients with adequately treated non-melanoma skin cancer, superficial bladder cancer and patients with prior history of malignancy who have been disease free for more than 3 years are eligible

    *Documented progressive mCRPC was based on at least one of three criteria: serum PSA progression, soft-tissue progression or bone disease progression. Serum PSA progression was defined as two consecutive increases in PSA over a previous reference value measured at least one week prior, minimal start value is 
2.0 ng/mL. Soft tissue progression was defined as an increase of ≥20% in the sum of the diameter (SOD) of all target lesions based on the smallest SOD since treatment started or the appearance of one or more new lesions. Progression of bone disease was defined as evaluable disease or new bone lesion(s) by bone scan (2+2 PCWG3 criteria).5,7

    †PSMA-positive disease sites were defined as ≥1 PSMA-positive lesions anywhere in the body, with PSMA positron emission tomography (PET) imaging ligand uptake greater than that of liver parenchyma in one or more metastatic lesions in any organ system. No size criteria were applied on PSMA-positive lesions.5
    ‡The study protocol is not the same as the licensed posology. Please refer to the Pluvicto SmPC for full details on the licensed posology.1
    §Imaging-based PFS was defined as the time from randomisation to independently centrally-reviewed disease progression (defined according to the PCWG3 criteria)7 or death.5
    First SSE defined as first new symptomatic pathological bone fracture, spinal cord compression, tumour-related orthopaedic surgical intervention, requirement for radiation therapy to relieve bone pain or death from any cause, whichever occurred first.5
    ‖Additional secondary endpoints included: safety and tolerability; health-related quality of life (HRQoL): 5-level EuroQol-5 dimension version (EQ-5D-5L), functional assessment of cancer therapy-prostate (FACT-P) and brief pain inventory (short form) (BPI-SF); health economics; composite PFS (radiological, clinical or PSA progression); biochemical response (PSA, alkaline phosphatase and lactate acid dehydrogenase levels).5

    pluvicto-clinical-trials-vision-tab1-graph2.png
    pluvicto-clinical-trials-vision-tab1-graph3.png

    *Data are from patients randomised after implementation of enhanced study site education, N=581.5

    pluvicto-clinical-trials-vision-tab2-graph1.png
    pluvicto-clinical-trials-vision-tab2-graph2.png
    pluvicto-clinical-trials-vision-tab2-graph3.png

    *The FACT-P is made up of 2 parts: the functional assessment of cancer therapy-general (FACT-G) questionnaire with 27 questions, and the prostate cancer subscale (PCS) with an additional 12 questions. The FACT-G (functional assessment of cancer therapy general) questionnaire is one of the most widely used HRQoL instruments and measures HRQoL in four different domains: physical well-being, functional well-being, emotional well-being, and social/family well-being. The PCS is designed specifically to measure prostate cancer QoL. The total score is the sum of the scores of 39 items of the questionnaire and ranges from 0156, with higher scores indicating better QoL. Assessments may be either self-completed by the subject or administered via face-to-face interview and completed by a caretaker/clinician.5
    †Data are from patients randomised after implementation of enhanced study site education, N=581.5
    ‡Time to pain worsening of 30% or greater or 2 points or greater in BPI-SF pain intensity, clinical disease progression or death.5

    pluvicto-clinical-trials-vision-tab4-graph1.png

    *Data are from patients randomised after implementation of enhanced study site education, N=581.5
    †OR=11.19 (95% CI: 6.25–20.04).5
    ‡OR=23.62 (95% CI: 8.57–65.11).5

The safety of Pluvicto was evaluated in two trials, PSMAfore and VISION. In PSMAfore, the most common (≥20%) adverse drug reactions (ADRs) occurring in patients who received Pluvicto include: dry mouth (60.8%), fatigue (52.9%), nausea (31.7%), anaemia (27.3%), constipation (22.0%), and decreased appetite (21.6%). The most common grade 3 to 4 ADRs (≥5%) occurring in patients who received Pluvicto include: anaemia (6.2%).1
In VISION, the most common (≥20%) ADRs occurring at a higher incidence in patients who received Pluvicto + BSoC compared to BSoC alone include: fatigue (48.0%), dry mouth (39.3%), nausea (35.7%), anaemia (31.9%), decreased appetite (21.4%) and constipation (20.2%). The most common grade 3 to 4 ADRs (≥5%) occurring at a higher incidence in patients who received Pluvicto + BSoC compared to BSoC alone include: anaemia (12.9%), thrombocytopenia (7.9%), lymphopenia (7.8%) and fatigue (6.6%).1

This list is not exhaustive; for further safety information, please refer to the SmPC.

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177Lu, lutetium-177; ADR, adverse drug reaction; AIDS, acquired immunodeficiency syndrome; AR, androgen receptor; ARPI, androgen receptor pathway inhibitor; ARDT, androgen receptor-derived therapies; AR-V7, androgen receptor splice variant-7; AV, atrioventricular; BM, bone marrow; BPI-SF, brief pain inventory (short form); BSoC, best standard of care; BRCA, breast cancer gene; CABG, coronary artery bypass graft; CI, confidence interval; CNS, central nervous system; COVID-19; coronavirus disease 2019; CT, computed tomography; DCR, disease control rate; ECG, electrocardiogram; ECOG-PS, Eastern Cooperative Oncology Group performance status; EQ-5D-5L, 5-level EuroQol-5 dimension version; FACT-G, functional assessment of cancer therapy-general; FACT-P, functional assessment of cancer therapy-prostate; 68Ga-PSMA-11, gallium-68–labelled prostate-specific membrane antigen ligand 11; HR, hazard ratio; HRQoL, health-related quality of life; IQR, interquartile range; ITT, intention-to-treat; LHRH, luteinising hormone releasing hormone; mCRPC, metastatic castration-resistant prostate cancer; MI, myocardial infarction; MRI, magnetic resonance imaging; NE, not estimable; ORR, objective response rate; OS, overall survival; PARP, poly (ADP-ribose) polymerase; PCS, prostate cancer subscale; PCWG3, Prostate Cancer Clinical Trials Working Group 3; PET, positron emission tomography; PFS, progression-free survival; PSA, prostate-specific antigen; PSMA, prostate-specific membrane antigen; QoL, quality of life; 223Ra, radium-223; R, randomisation; RECIST, Response Evaluation Criteria in Solid Tumors; RLT, radioligand therapy; rPFS, radiographic progression-free survival; SmPC, summary of product characteristics; SOD, sum of diameter; SSE, symptomatic skeletal event. 

References

  1. Pluvicto®▼ (lutetium [177Lu] vipivotide tetraxetan) Summary of Product Characteristics.

  2. Locametz®▼ (gozetotide) Summary of Product Characteristics.

  3. Morris MJ, et al. Lancet 1.2024;404:12271239 and supplementary appendices 1 and 2.

  4. Fizazi K, et al. Ann Oncol 2025;36(11):1319–1330.

  5. Sartor O, et al. N Engl J Med 2021;385(12):1091–1103 and supplementary appendix and protocol.

  6. Fizazi K, et al. Lancet Oncol 2023;24(6):597–610.

  7. Scher HI, et al. J Clin Oncol 2016;34(12):14021418.

  8. Fizazi K, et al. Ann Oncol 2021;32(Supplement 5):S626–S677.

 

UK | April 2026 | FA-11470195-2

Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis online through the pharmacovigilance intake (PVI) tool at www.novartis.com/report, or alternatively email [email protected] or call 01276 698370.