Title: A Phase IV, Post-Authorization Safety Study to Investigate the Long-Term Safety of Lutetium (177Lu) Vipivotide Tetraxetan in Adult Participants With Prostate Cancer.

Description: This long-term study aims to investigate the long-term risks and potential side effects of the drug 177Lu Vipivotid Tetraxetan (AAA617) across multiple study centers. The goal is to more precisely characterize known and potential risks and to monitor serious adverse events over time. The study is intended for adults with prostate cancer who have received at least one dose of AAA617 in a Novartis-sponsored clinical trial (Phase I–IV).

Study Procedure: This is a purely observational study lasting up to 10 years, with regular follow-up visits every 6 to 8 months to monitor adverse events and laboratory values.

Objectives: The long-term observation aims to collect information on the safety and potential side effects of AAA617, in order to better evaluate the treatment with this drug in the future.

Inclusion Criteria:

• Signed informed consent must be obtained prior to participation in the study.

• Participants must have received at least one dose of AAA617 in an interventional Phase I–IV prostate cancer study sponsored by Novartis and have fulfilled the requirements of that trial that allow participation in this follow-up study.

Title: An International Prospective Open-label, Randomized, Phase III Study Comparing 177Lu-PSMA-617 in Combination With SoC, Versus SoC Alone, in Adult Male Patients With mHSPC (PSMAddition).

Description: This study investigates whether the combination of 177Lu-PSMA-617 with standard therapy (Androgen Receptor Pathway Inhibitor (ARPI) + Androgen Deprivation Therapy (ADT)) improves progression-free survival compared to standard therapy alone in patients with metastatic hormone-sensitive prostate cancer (mHSPC). The total study duration is 50 months.

Study Procedure: Before starting therapy, a screening is performed to assess eligibility, including a 68Ga-PSMA PET/CT scan to evaluate PSMA expression. Eligible participants are then randomly assigned to one of two treatment groups: standard therapy alone or 177Lu-PSMA-617 combined with standard therapy. After completion of the therapy, there is a follow-up period of approximately 12 months to assess safety and efficacy, followed by regular long-term monitoring.

Title: An International Prospective Open-label, Multi-center, Randomized, Non-comparative Phase II Study of Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) Alone and Lutetium [177Lu] Vipivotide Tetraxetan (AAA617) in Combination With Androgen Receptor Pathway Inhibitors in Patients With PSMA PET Scan Positive Castration-Resistant Prostate Cancer.

Description: This study is designed to evaluate the efficacy and safety of 177Lu Vipivotide Tetraxetan (AAA617) alone and in combination with an Androgen Receptor Pathway Inhibitor (ARPI) in patients with non-metastatic castration-resistant prostate cancer. Participants are randomly assigned to one of two groups: AAA617 alone or AAA617 in combination with the ARPI.

Inclusion Criteria: 

• Participants must be 18 years or older and have provided signed informed consent prior to study participation.

• Histologically or cytologically confirmed prostate cancer.

• Participants must be receiving ongoing androgen deprivation therapy (ADT) with a GnRH agonist/antagonist or have had a prior bilateral orchiectomy at the time of randomization. Intermittent ADT before randomization is acceptable if the serum testosterone criterion is met.

• Castrate level of serum testosterone (< 1.7 nmol/L [50 ng/dL]) on GnRH agonist or antagonist therapy (continuous or intermittent) or after bilateral orchiectomy prior to randomization.

• Evidence of PSMA-positive disease (N1 or M1) on baseline PET/CT scan with AAA517 or Piflufolastat F18, as determined by Blinded Independent Central Review (BICR) based on the Prostate Cancer Molecular Imaging Standardized Evaluation (PROMISE) methodology (Eiber et al., 2018). Participants with M1 disease only visible on PSMA PET are eligible.

• Conventional imaging must be negative for M1 disease.

• Participants must have adequate organ function, including bone marrow reserve, liver, and kidney function.

Title: An International, Prospective, Open-label, Multi-center, Randomized Phase III Study Comparing Lutetium (177Lu) Vipivotide Tetraxetan (AAA617) Versus Observation to Delay Castration or Disease Recurrence in Adult Male Patients With Prostate-specific Membrane Antigen (PSMA) Positive Oligometastatic Prostate Cancer (OMPC).

Description: This study aims to evaluate the efficacy and safety of 177Lu Vipivotide Tetraxetan (AAA617) in patients with oligometastatic prostate cancer (OMPC) whose tumor progresses after definitive primary therapy. The goal is to prevent progression to lethal metastatic disease and maintain quality of life by delaying therapy with androgen deprivation therapy (ADT).

Study Procedure: Before therapy, a 68Ga-PSMA PET/CT screening and other assessments are performed. Subsequently, stereotactic body radiotherapy (SBRT) is administered over approximately 3 weeks. After SBRT, participants are randomly assigned to one of two groups. One treatment group receives up to 4 cycles of AAA617 therapy, while the control group undergoes observation only following SBRT.

During AAA617 therapy, participants undergo monitoring during weeks 1 and 3 of each cycle. For both groups, follow-up visits occur every 16 weeks after the end of therapy. The total study duration is approximately 6.5 years.

Inclusion Criteria:

• Histologically confirmed prostate cancer prior to randomization.

• Biochemical recurrence after definitive primary therapy of the prostate (Radical Prostatectomy (alone or with post-operative radiation), External Beam Radiation Therapy (prostate ± seminal vesicles ± pelvic lymph nodes), or brachytherapy).

• Oligometastatic disease: 1–5 PSMA-positive metastases on PSMA PET/CT (Ga-68 Gozetotide or F-18 Piflufolastat), with at least one lesion being a distant metastasis (M1) according to AJCC8.

• Conventional imaging (CT/MRI and bone scintigraphy) must be negative for M1 metastases.

• Serum testosterone in the non-castrated range (>100 ng/dL) at screening.

Title: Prospective, Multi-Center Study to Assess the DIagnostic Performance of [18F]PSMA-1007 PET/CT Imaging in Patients with Newly-DIagnosed High-Risk or Very-High-Risk Prostate Cancer.

Description: This study aims to evaluate the sensitivity and specificity of [18F]PSMA-1007 positron emission tomography combined with computed tomography (PET/CT) for detecting pelvic lymph node metastases (N1) in newly diagnosed high-risk or very-high-risk prostate cancer.

Inclusion Criteria:

• Patients with newly diagnosed prostate cancer who are initially planned to undergo surgery for removal of the prostate and pelvic lymph nodes.

• Conventional imaging must have been performed within 60 days prior to the planned study.

Title: A Phase I, open-label, multi-center exploratory safety and efficacy study with PSMA, SSTR2 and GRPR targeted radioligand therapy in metastatic neuroendocrine prostate cancer.

Description: The aim of this study is to investigate a new targeted treatment approach for patients with metastatic neuroendocrine prostate cancer (mNEPC). Three potential target proteins are evaluated: PSMA, SSTR2 (somatostatin receptor 2), and GRPR (gastrin-releasing peptide receptor).

Study Procedure: PET/CT scans are used in advance to determine whether the cancer cells express any of these proteins, which helps assign patients to a specific study group and therapy. Treatment is performed using a Lutetium-177 (177Lu)-based radiopharmaceutical. The drug specifically binds to the identified target protein and destroys cancer cells directly through high-energy radiation.

Participants are assigned to one of the following therapy groups depending on the target protein:

177Lu-PSMA-617 for PSMA-positive cells
177Lu-DOTA-TATE for SSTR2-positive cells
177Lu-NeoB for GRPR-positive cells

Treatment is administered every 6 weeks for up to 36 weeks. During therapy, regular assessments including MRI, SPECT, and additional PET/CT scans are performed to monitor efficacy.

Inclusion Criteria:

• Participants must have metastatic prostate cancer with neuroendocrine differentiation.

• PSMA- and/or SSTR2- and/or GRPR-positive PET scan with at least one measurable lesion according to RECIST 1.1 and moderate target expression in at least one of the three PET scans.

• Castrate level of serum/plasma testosterone (< 50 ng/dL or < 1.7 nmol/L) for participants with an adenocarcinoma component, or stable testosterone levels for participants with pure neuroendocrine carcinoma.

• Recovery to grade 2 or lower from all clinically significant toxicities related to prior therapy.

• Adequate bone marrow and organ function as assessed by a central laboratory for study eligibility.

• ECOG performance status of 2 or lower.

Title: VISION: An International, Prospective, Open Label, Multicenter, Randomized Phase 3 Study of 177Lu-PSMA-617 in the Treatment of Patients With Progressive PSMA-positive Metastatic Castration-resistant Prostate Cancer (mCRPC).

Description: This phase III study aims to evaluate the efficacy and safety of 177Lu-PSMA-617 in patients with progressive PSMA-positive metastatic castration-resistant prostate cancer (mCRPC). The primary objectives of the study are: 1. comparison of overall survival between patients receiving 177Lu-PSMA-617 plus standard therapy and patients receiving standard therapy alone, and 2. radiographic progression-free survival. Other parameters being assessed include tumor response, time to first symptomatic skeletal event, safety, quality of life, and health economics.

Study Procedure: Patients with PSMA-positive scans are randomly assigned to one of two groups. The first group receives 177Lu-PSMA-617 plus standard therapy, and the second group receives standard therapy alone. The treatment duration is 6–10 months, with a maximum of 6 cycles, administered every 6 weeks. After 4 cycles, a check is performed to determine if further cycles should be given. Imaging assessments are conducted every 8 weeks during the first 24 weeks and every 12 weeks thereafter. Blood tests are performed at specific time points. After completion of therapy, follow-up visits are scheduled every 3 months for over 2 years. The standard therapy is determined individually for each patient.

Title: Efficacy of Personalised Irradiation with Rhenium-Skin Cancer Therapy (SCT) for the treatment of non-melanoma skin cancer; a phase IV multi-centre, international, open label, single arm study.

Description: This study evaluates the efficacy and safety of Rhenium-SCT® in the treatment of non-melanoma skin cancer (NMSC). The primary objective of the study is to assess the effectiveness of Rhenium-SCT® in treating NMSC. Additional objectives include evaluating changes in participants’ quality of life before treatment and at 6 and 12 months after treatment, assessing treatment comfort from the participants’ perspective, and evaluating the cosmetic outcomes after treatment.

Study Procedure: Rhenium-188 (188Re), a beta-emitter whose high-energy radiation is used for therapeutic purposes with limited penetration depth, is used in the therapy. This allows targeted treatment of superficial tissue. The skin area to be treated is marked and covered with a protective film. The radioactive substance is then precisely applied directly over the tumor using an applicator. The treatment duration is approximately 30 to 180 minutes, after which the protective film containing the radioactive material is removed.

Title: Phase Ib Dose Finding Study Assessing Safety and Activity of [177Lu]Lu-NeoB in Combination With Radiotherapy and Temozolomide in Subjects With Newly Diagnosed Glioblastoma and as a Single Agent in Recurrent Glioblastoma.

Description:
This study investigates a therapeutic approach using Lutetium-177 (177Lu). The aim is to evaluate the safety and efficacy of 177Lu-NeoB in combination with radiotherapy and temozolomide (TMZ) in patients with newly diagnosed glioblastoma, as well as 177Lu-NeoB as a monotherapy in recurrent glioblastoma. Additionally, the safety and uptake of the PET imaging agent (68Ga-NeoB) will be assessed.

177Lu is a beta-emitter used for therapeutic purposes, delivering high-energy radiation to damage and destroy tumor tissue. Gallium-68 emits positrons (β+), which can be used for PET imaging.

Newly Diagnosed Glioblastoma: In patients with newly diagnosed glioblastoma, the recommended dose of 177Lu-NeoB in combination with TMZ and radiotherapy will be determined, and the safety and tolerability of the therapy will be assessed. The radioactive agent is administered every 4 weeks, for a total of 6 applications, with the possibility of up to 4 additional applications. Weekly examinations are performed during this period. The efficacy of the therapy is evaluated every 8 weeks using contrast-enhanced MRI. After therapy, follow-up visits are conducted for up to 5 years.

Recurrent Glioblastoma: In patients with recurrent glioblastoma, the recommended dose of 177Lu-NeoB as monotherapy will be determined, and safety and tolerability will be assessed. In addition, the presence of GRPR in the glioblastoma will be examined using 68Ga-NeoB PET. 177Lu-NeoB is administered every 3 weeks for a total of 6 applications, with the possibility of up to 4 additional applications.

General Inclusion Criteria:

• Signed informed consent must be obtained prior to participation.
• Age ≥ 18 years.
• Histologically confirmed glioblastoma according to WHO classification, established after surgical resection or biopsy.
• Participants receiving corticosteroid treatment with dexamethasone must be treated with a dose ≤ 4 mg/day (or equivalent doses of other corticosteroids) for at least 7 days prior to study treatment initiation.
• Adequate bone marrow and organ function.

Title: PRRT in Germany – Use of Peptide Receptor Radionuclide Therapy (PRRT) in patients with neuroendocrine tumors (NET) in Germany – A retrospective analysis of the treatment pathway of GEP-NET patients in German NET treatment centers.

Description: In this study, retrospective existing patient data on the use and frequency of PRRT with 177Lu-DOTATATE in patients with GEP-NET will be collected and analyzed. The study is conducted nationally in treatment centers for NETs.