Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication PLUVICTO is indicated for the treatment of adult patients with prostate-specific membrane antigen (PSMA)-positive metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor pathway inhibitor (ARPI) therapy, and are considered appropriate to delay taxane-based chemotherapy, or have received prior taxane-based chemotherapy. FDA label
Also known as [177Lu]Lu-PSMA-617, Lu-PSMA-617, 177Lu-PSMA-617, AAA617, 177Lu-PMSA-617, 177Lu-labeled PSMA-617, Lu177-PSMA-617, Lutetium Lu 177-PSMA-617
Lutetium Lu 177 Vipivotide Tetraxetan · 19 trials · 21 indications
Overall survival (OS) is defined as the time from the date of randomization to the date of death due to any cause.
Radiographic progression-free survival (rPFS) is defined as the time from randomization to the date of radiographic progression according to PCWG3 criteria by investigator assessment, or death, whichever occurs first.
Blinded Independent Review Committee (BIRC) assessed Metastasis Free Survival (MFS) is defined as the time from randomization to first evidence of radiographically detectable bone or soft tissue distant metastasis by conventional imaging (i.e., Computed Tomography (CT)/Magnetic Resonance Imaging (MRI) and bone scans) as assessed by BIRC using RECIST 1.1 or death due to any cause, whichever occurs first. Participants who are alive without distant metastasis at the analysis data cut-off or are lost to follow-up at the time of analysis will be censored for MFS at the time of their last adequate radiographic assessment. Clinical deterioration without objective radiographic evidence will not be considered as documented distant metastasis.
rPFS is defined as the time to radiographic progression by Prostate cancer working Group 3 (PCWG3)-modified RECIST v1.1 as assessed by Blinded independent central (BICR) review or death.
PSA progression is defined as a rise in PSA at \> 12 weeks by more than 25% and more than 2ng/mL above the nadir (lowest PSA point). Time-to-event endpoints will be analyzed graphically and numerically using the Kaplan-Meier method and summarized in terms of median or 1-year survival point estimates with corresponding 95% confidence intervals.
Study is feasible if at least 1 PSMA-PET positive lesion is identified in at least 50% of the participants in this cohort
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
ORR is defined as the proportion of participants who experienced complete response (CR) or partial response (PR) during treatment. Tumors will be assessed for response and progression by RECIST version 1.1 by central radiology review.
Will be calculated as the percentage with 95% confidence interval (CI) of the total number of patients who had PSMA-high expression on re-assessment gallium Ga 68 gozetotide (68Ga)-PSMA-11 positron emission tomography (PET).
The absorbed dose in kidneys and selected organs will be summarized with descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Blood concentration of \[177Lu\]Lu-PSMA-617 will be summarized with descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. The half-live will be listed and summarized using descriptive statistics
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUC(0-inf) will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
Change from baseline of eGFR will be summarized for each post-dose (post-baseline) timepoint. The summary includes table with descriptive statistics at baseline, post-baseline time points and change from baseline to post-baseline timepoints.
Dose modifications (dose interruptions and reductions) for AAA617 will be assessed and summarized using descriptive statistics.
Dose intensity for AAA617 will be assessed and summarized using descriptive statistics.
PSA response is defined as the time of PSA nadir value of =\< 0.2 ng/mL is confirmed by a second (the next) PSA measurement at least 4 weeks later
Confirmed Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR). ORR is based on PCWG3-modified RECIST v1.1 response for patients with measurable disease at baseline.
A Dose Limiting Toxicity (DLT) is defined as any toxicity not attributable to the disease or disease-related processes under investigation, the time window for DLT assessment period is Cycle 1. To be considered a DLT, it must be related to 177Lu-PSMA-617 while fulfilling one of the criteria as per the NCI Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
Overall Response Rate (ORR) is defined as the proportion of participants with Best Overall Response (BOR) of Complete Response (CR) or Partial Response (PR) according to PCWG3 modified RECIST 1.1.
Treatment emergent adverse events will be classified according to the NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Adverse events and clinically significant laboratory abnormalities (meeting Grade 3, 4, or 5 criteria according to CTCAE) will be summarized by maximum intensity and relationship to Lu-PSMA-617 and liver-directed therapy (if applicable). Descriptive statistics will be utilized to display the data on toxicity seen. Descriptive summaries of discrete data will present the number of study participants and the incidence as a frequency and a percentage.
In GBq, cumulative and average per cycle.
Subacute AESIs are: * treatment-related grade 3-4 thrombopenia persisting more than 12 weeks * treatment-related grade 3-4 neutropenia persisting more than 12 weeks * treatment-related creatinine elevation to \>2x baseline and \>ULN (upper limit of normal) persisting more than 12 weeks * treatment-related grade 4 febrile neutropenia * treatment-related grade 4 non-hematological toxicity
Time activity curve (TAC) will be generated from the amount radioactivity in one given tissue. Time integrated activity coefficient and absorbed dose will be calculated
The distribution of adverse events for Radioligand Therapy (RLT) will be done via the analysis of frequencies for Adverse Event (AEs) and Serious Adverse Event (SAEs) through the monitoring of relevant clinical and laboratory safety parameters. Adverse event monitoring should be continued for at least 42 days following the end of treatment (EOT) visit. Participants receiving the study treatment will continue to be followed for safety every 12 weeks during the long-term follow-up for selected adverse events
The assessment of tolerability will be based on the frequency of participants with dose interruptions, reductions, and study treatment discontinuations. Dose reduction will be based on the worst toxicity demonstrated at the last dose.
The RP2D will be the highest administered dose level with ≤1 dose-limiting toxicities (DLTs) out of 6 treated patients.
| Arm | Type | Description |
|---|---|---|
| Arm A (Control arm): Standard of Care (SoC) alone | ACTIVE_COMPARATOR | The SoC is defined as one the following treatment which was initiated 6 to 8 months ahead of inclusion in this trial and still ongoing at the time of the randomization and continued at least until the CRPC stage is reached.: * ADT with an ARSI (i.e. abiraterone + prednisone, or apalutamide, or enzalutamide) ± radiotherapyª * ADT with docetaxelᵇ plus an ARSI (i.e. abiraterone + prednisone, or darolutamide,) ± radiotherapyª ª Radiotherapy can be part of any standard treatment aforementioned as long as it is not PSMA-based and completed at least 4 weeks ahead of randomization OR planned right after randomization in arm A. ᵇ Whenever docetaxel was part of the systemic treatment initiation, its administration must have been completed at least 4 weeks ahead of randomization. |
| Arm B (Experimental arm): 177Lu-PMSA-617 + SoC | EXPERIMENTAL | Once every 6 weeks, 7400 MBq 177Lu-PMSA-617 will be administered for up to a total of 4 cycles. Upon 177Lu-PMSA-617 treatment completion, the ongoing standard systemic treatment is to be maintained and continued at least until the CRPC stage is reached. The SoC is defined as one the following treatment which was initiated 6 to 8 months ahead of inclusion in this trial and still ongoing at the time of the randomization: * ADT with an ARSI (i.e. abiraterone + prednisone, or apalutamide, or enzalutamide) ± radiotherapyª * ADT with docetaxelᵇ plus an ARSI (i.e. abiraterone + prednisone, or darolutamide,) ± radiotherapyª ª Radiotherapy can be part of any standard treatment aforementioned as long as it is not PSMA-based completed at least 4 weeks ahead of randomization OR planned right after 177Lu-PSMA-617 in arm B. ᵇ Whenever docetaxel was part of the systemic treatment initiation, its administration must have been completed at least 4 weeks ahead of randomization. |
| Investigational Arm: lutetium (177Lu) vipivotide tetraxetan (AAA617) | EXPERIMENTAL | All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by a dose of 7.4 GBq (200 mCi) +/- 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for a planned 4 cycles. |
| Control arm: observation (watchful waiting) | NO_INTERVENTION | All participants will be treated with Stereotactic Body Radiation Therapy (SBRT) to all metastatic lesions followed by observation only. |
| 177Lu-PSMA-617 | EXPERIMENTAL | Participants received 7.4 GBq (200 mCi) +/- 10% 177Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT could be used. |
| Androgen receptor-directed therapy (ARDT) | ACTIVE_COMPARATOR | For participants randomized to the ARDT arm, abiraterone or enzalutamide was administered per the physician's orders. Best supportive care, including Androgen deprivation therapy (ADT) could be used. |
| Standard of Care | ACTIVE_COMPARATOR | For participants randomized to Standard of Care arm, ARDT +ADT is considered as SOC and treatment will be administered per the physician's order |
| Treatment (177Lu-PSMA-617) | EXPERIMENTAL | Patients receive 177Lu-PSMA-617 IV over 30 minutes on days 1, 8, 50, 57, 99 and 141. Treatment repeats every 7 days for cycles 1 and 3 and every 6 weeks for cycle 2 and subsequent cycles for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo PSMA-PET/CT during screening and SPECT/CT on study. Patients also undergo CT or MRI, bone scan, as well as blood sample collection throughout the study. |
| Treatment (Pluvicto) | EXPERIMENTAL | Patients receive Pluvicto IV on day 1 of each cycle. Cycles repeat every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients also undergo PSMA PET scan, CT scan, bone scan, collection of blood samples, and optional SPECT scans and pre- and post-treatment biopsies. |
| Lu-PSMA-617 | EXPERIMENTAL | Participants will receive 177Lu-PSMA-617 7.4 GBq (200 mCi) once every 6 weeks. 177Lu-PSMA-617 is a radiopharmaceutical which will be administered intravenously (IV). |
| Arm A: AAA617 and ARPI (Abiraterone or Enzalutamide) | EXPERIMENTAL | 4 participants to receive AAA617 in combination with ARPI |
| Arm B: AAA617 alone | ACTIVE_COMPARATOR | 3 participants will receive AAA617 alone. |
| Experimental: 177Lu-PSMA-617 | EXPERIMENTAL | Enrolled participants will complete: * Baseline visit --Imaging every 12 weeks, or 2 cycles * Cycles 1 through 2: * Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * PSMA PET scan before Cycle 3 Day 1 * Cycles 3 through 6: --Day 1: Predetermined dose of 177Lu-PSMA-617 1x daily * End of treatment visit with assessments * Follow Up: every 6 months for up to 5 years * If no radiographic responses of Complete or Partial Response are seen in the first 9 participants enrolled, the trial will terminate. If 1 or more responses are seen in the first 9 participants, the study will enroll an additional 15 participants. |
| Treatment (vorinostat, 177Lu-PSMA-617) | EXPERIMENTAL | Patients receive vorinostat PO QD for 28 days and then receive gallium Ga 68 gozetotide IV and undergo a PET scan on trial. Patients may go on to receive 177Lu-PSMA-617 IV per SOC on day 1 of each cycle. Treatment repeats every 6 weeks for up to 6 cycles in the absence of disease progression or unacceptable toxicity. Patients undergo CT and bone scan on trial and during follow-up, as well as a FDG PET/CT during screening and on trial and SPECT/CT on trial. Patients undergo blood sample collection on trial and may also optionally undergo biopsy during screening and on trial. |
| AAA617 | EXPERIMENTAL | Participants will receive a dose of 7.4 GBq (200 mCi) ± 10% of AAA617 which will be administered once every 6 weeks (1 cycle) for up to 6 cycles if enrolled in Cohorts A or B. Participants with severe renal impairment (in cohort C) will receive a dose of 7.4 GBq of AAA617 for up to 3 cycles of treatment. Based on the emerging safety data and if the investigators deem the participant is still benefiting from study drug, 3 additional cycles may be administered for Cohort C participants. |
| Arm A | EXPERIMENTAL | Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. ADT must be ongoing; Best supportive care is allowed. |
| Arm B | EXPERIMENTAL | Participants will receive 7.4 GBq (+/- 10%) of AAA617 (Lutetium \[177Lu\] vipivotide tetraxetan) once every 6 weeks for 6 cycles. In addition of SOC (ADT plus choice of ARPI as per physician's decision), Best supportive care is allowed. |
| [177Lu]Lu-PSMA-617 plus best supportive/best standard of care (BS/BSOC) | EXPERIMENTAL | Patients received the investigational product 7.4 GBq (+/- 10%) 177Lu-PSMA-617 intravenously every 6 weeks (+/- 1 week) for a maximum of 6 cycles. Best supportive/best standard of care (BS/BSOC) could be used. |
| [177Lu]Lu-PSMA-617 | EXPERIMENTAL | Participants will receive 7.4 GBq (200 mCi) +/- 10% \[177Lu\]Lu-PSMA-617 once every 6 weeks for 6 cycles. Best supportive care, including ADT may be used. |
| Personalized activity | EXPERIMENTAL | - |
| Fixed activity | ACTIVE_COMPARATOR | - |
| Phase 1A: Dose Escalation | EXPERIMENTAL | Participants will be enrolled in a 3+3 dose escalation design to establish a maximum tolerated dose (MTD) of carboplatin, starting at Dose Level 1 and escalating to Dose Level 2 or 3. * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42-day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42-day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. If 0 out of 3 participants experience a dose-limiting toxicity (DLT), the study will proceed to the next dose level. If 1 or more participants experience a DLT, this dose level is declared the MTD and study will not proceed to expansion. If 1 out of 6 participants at the highest dose level experience DLTs, this is the recommended Phase 1B dose. |
| Phase 1B: Dose Expansion | EXPERIMENTAL | 19 additional participants will be enrolled at the RP2D of carboplatin and will complete: * Baseline visit. * Day 1 of Cycles 3 and 5: Tumor assessment radiologic scans. * Tumor biopsy at baseline and at 12 weeks. * Cycle 1 through End of Treatment: * Days 1 and 22 of 42 day cycle: Predetermined dose of carboplatin every 3 weeks for a maximum of up to 6 cycles. * Day 2 of 42 day cycle: Predetermined dose of 177Lu-PSMA-617 every 6 weeks for a maximum of up to 6 cycles. * End of treatment visit. * Follow up visits in-office or via telephone. |
| Name | Type | Description |
|---|---|---|
| 177Lu-PMSA-617 | DRUG | Once every 6 weeks, 7400 MBq 177Lu-PMSA-617 will be administered for up to a total of 4 cycles. |
| Standard of Care | DRUG | ADT, abiraterone and each ARSI (Apalutamide, Darolutamide, Enzalutamide) will be administrated according to the standard of care |
| AAA617 | DRUG | Radiopharmaceutical solution for infusion/injection |
| piflufolastat (18F) | DRUG | Provided as ready-to-use radiopharmaceutical |
| gallium (68Ga) gozetotide (25μg) | DRUG | Provided as PSMA-11 Kit for radiopharmaceutical preparation of gallium (68Ga) gozetotide |
| 177Lu-PSMA-617 | DRUG | administered intravenously once every 6 weeks (1 cycle) for 6 cycles |
| 68Ga-PSMA-11 | DRUG | single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 185 MBq (3 - 5 mCi). |
| ARDT | DRUG | administered orally on a continuous basis, as per package insert and guidelines |
| ADT | DRUG | ADT are administered as per physician order |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Bone Scan | PROCEDURE | Undergo bone scan |
| Computed Tomography | PROCEDURE | Undergo SPECT/CT and CT |
| Lutetium Lu 177 Vipivotide Tetraxetan | DRUG | Given IV |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| PSMA PET-CT Scan | PROCEDURE | Undergo PSMA PET/CT |
| Questionnaire Administration | OTHER | Ancillary studies |
| Single Photon Emission Computed Tomography | PROCEDURE | Undergo SPECT/CT |
| Biopsy Procedure | PROCEDURE | Undergo biopsy |
| PSMA PET Scan | PROCEDURE | Undergo PSMA PET scan |
| Lu-PSMA-617 | DRUG | Given IV |
| ARPI: Abiraterone | DRUG | Dose formulation: tablet/capsule Dose level: 160 mg (four 40 mg soft capsules or four 40 mg tablets or two 80 mg tablets) as a single daily dose, oral administration |
| ARPI: Enzalutamide | DRUG | Dose formulation: tablet Dose level: 1000 mg daily (two 500 mg tablets or four 250 mg tablets as a single daily dose together with 5 mg oral prednisone 2 times a day, oral administration |
| Fludeoxyglucose F-18 | OTHER | Undergo FDG PET/CT |
| Gallium Ga 68 Gozetotide | OTHER | Given IV |
| Positron Emission Tomography | PROCEDURE | Undergo 68Ga-PSMA-11 PET |
| Vorinostat | DRUG | Given IV |
| AAA517 | DRUG | Single intravenous dose of approx. 150 Megabecquerel (MBq) prior PSMA-PET scans |
| Piflufolastat F 18 | DRUG | Single intravenous dose of approx. 333 Megabecquerel (MBq) prior PSMA-PET scans |
| ARPI | DRUG | Enzalutamide, Darolutamide, Apalutamide as prescribed by the local investigator |
| Best supportive care | OTHER | as prescribed by the local investigator |
| [177Lu]Lu-PSMA-617 | DRUG | Administered intravenously once every 6 weeks (1 cycle) for a maximum of 6 cycles. |
| Best supportive/best standard of care (BS/BSOC) | OTHER | Best supportive/best standard of care as defined by the local investigator |
| [68Ga]Ga-PSMA-11 | DRUG | single intravenous dose of approximately 150 MBq. Administered dose must not be lower than 111 MBq or higher than 259 MBq (3 - 7 mCi). |
| Best supportive/best standard of care | OTHER | Best supportive/best standard of care as defined by the local investigator (Post taxane population only) |
| Ablation | PROCEDURE | Undergo ablation |
| Trans-arterial chemoembolization (TACE) | PROCEDURE | Undergo TACE |
| Positron Emission Tomography (PET)/Computerized tomography (CT) | PROCEDURE | Undergo imaging |
| Tumor Biopsy | PROCEDURE | Undergo biopsy |
| Questionnaire | OTHER | Participant will complete questionnaire |
| Gonadotropin-releasing hormone (GnRH) analogues | DRUG | Anatomical Therapeutic Chemical \[ATC\] code L02AE |
| Gonadotropin-releasing hormone (GnRH) antagonists | DRUG | Degarelix, Relugolix |
| Carboplatin | DRUG | Platinum coordination compound, premixed aqueous solution of 10mg/ML, via intravenous (into the vein) infusion per protocol. |
Inclusion Criteria: All of the following criteria must be met ahead of randomization to satisfy trial eligibility requirements: 1. Signed a written informed consent form prior to any trial specific procedures. Note: In case of physical incapacitation, a trusted representative of their choice, ...
Lutetium Lu 177 Vipivotide Tetraxetan is an investigational radiopharmaceutical developed by Novartis AG (ticker NVS) for oncology. It is being studied in prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC), and in renal cell carcinoma. It is a small molecule binding agent that delivers radiation to cells expressing somatostatin receptors.
Lutetium Lu 177 Vipivotide Tetraxetan targets somatostatin receptors, specifically SSTR1, SSTR2, SSTR3, SSTR4 and SSTR5. It is classified as a binding agent, meaning the molecule binds these receptors and delivers its radioactive lutetium-177 payload to receptor-expressing cells. Trials are biomarker selected, enrolling patients whose tumors express the relevant target.
Novartis AG, which trades under the ticker NVS, is the developer of Lutetium Lu 177 Vipivotide Tetraxetan. Novartis is running the clinical program, which includes studies in metastatic castration-resistant prostate cancer and renal cell carcinoma across sites in the United States and Canada.
Lutetium Lu 177 Vipivotide Tetraxetan is in Phase 2 clinical development. Five trials are recorded for the program, four of them active and one completed, with total enrollment of about 1,658 participants. It is an investigational agent and has not been established as approved therapy in the studies tracked here.
Trials include NCT07860554, a Phase 2 study in African American men with metastatic castration-resistant prostate cancer; NCT07145177, a Phase 1 study combining it with liver directed therapy; NCT06964958, a Phase 2 study in renal cell carcinoma; and NCT06943495, the Phase 1 PRODIGY-2 study comparing personalized with fixed-activity dosing in Canada.
Yes. Lutetium Lu 177 Vipivotide Tetraxetan is also known as [177Lu]Lu-PSMA-617, Lu-PSMA-617, 177Lu-PSMA-617, AAA617 and 177Lu-PMSA-617. These names refer to the same investigational compound developed by Novartis, so search results and trial records using any of these labels describe the same asset.