Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
AAA617 · 5 trials · 5 indications
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.
Number of participants with adverse events (AEs) and serious adverse events (SAEs).
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
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.
| Arm | Type | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| Name | Type | Description |
|---|---|---|
| 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 |
| 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 |
| 68Ga-PSMA-11 | DRUG | Single intravenous dose of approximately 150 MBq |
| 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 |
| ADT | DRUG | as prescribed by the local investigator |
| Best supportive care | OTHER | as prescribed by the local investigator |
| Gonadotropin-releasing hormone (GnRH) analogues | DRUG | Anatomical Therapeutic Chemical \[ATC\] code L02AE |
| Gonadotropin-releasing hormone (GnRH) antagonists | DRUG | Degarelix, Relugolix |
Key Inclusion criteria: 1. Histologically confirmed prostate cancer prior to randomization 2. Participants must have biochemically recurrent disease after definitive treatment to prostate by Radical Prostatectomy ((RP), (alone or with post-operative radiation to prostate bed/pelvic nodes)) or Exter...
AAA617, also known as Lutetium (177Lu) Vipivotide Tetraxetan, is an investigational radiopharmaceutical being studied for the treatment of prostate cancer, including metastatic castration-resistant prostate cancer (mCRPC) and oligometastatic prostate cancer (OMPC). It is currently in clinical development and has not been approved by regulatory authorities.
AAA617 targets prostate-specific membrane antigen (PSMA), a protein highly expressed on prostate cancer cells. By delivering a radioactive isotope, Lutetium-177, to PSMA-positive tumors, the drug aims to deliver targeted radiation therapy to cancer cells while sparing normal tissue.
AAA617 is being developed by Novartis AG, a global pharmaceutical company listed on the New York Stock Exchange under the ticker symbol NVS. The company is conducting multiple clinical trials to evaluate the drug's safety and efficacy in various stages of prostate cancer.
AAA617 is in Phase 2 clinical development. While some trials listed under the drug name are Phase 1 and Phase 3, the most advanced stage for AAA617 itself is Phase 2, as indicated by the developer. It remains an investigational drug and is not yet approved for commercial use.
AAA617 is being evaluated in several clinical trials, including NCT05849298, a Phase 2 study of AAA617 alone and in combination with an androgen receptor pathway inhibitor (ARPI) in PSMA PET scan positive CRPC. Other trials include NCT05939414, a Phase 3 study in oligometastatic prostate cancer, and NCT06531499, a Phase 1 dosimetry study in mCRPC.
Yes, AAA617 is also known as Lutetium (177Lu) Vipivotide Tetraxetan. This alternative name appears in the titles of several clinical trials, including NCT05939414 and NCT06531499, and refers to the same investigational radiopharmaceutical compound.