Evaluation of Lutetium (177Lu) Vipivotide Tetraxetan in Recurrent/Metastatic Adenoid Cystic Carcinoma of Salivary Glands: Safety and Tolerability Study

The primary objective of this clinical trial is the **assessment of safety and tolerability** of treatment using a specialized prostate-specific membrane antigen (PSMA) labeled with Lutetium177 in patients with recurrent and/or metastatic adenoid cystic carcinoma originating from the salivary glands. This evaluation is conducted according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). The clinical relevance of this objective lies in determining the potential adverse effects and overall patient tolerance to the treatment, which is crucial for ensuring patient safety and optimizing therapeutic protocols.

The secondary objectives include the following assessments:

• **Objective response rate (ORR)**, evaluated via CT scan according to RECIST 1.1 score, two years post-treatment completion.
• **Progression-free survival (PFS)**, measured from the start of treatment to the time of disease progression or death.
• **Overall survival (OS)**, assessed from the start of treatment to the time of death.
• **Duration of response (DoR)**, evaluated from study inclusion to progression or death in patients who achieved a complete or partial response, applicable only to patients in remission.
• **Quality of life assessment**, conducted using the EORTC QLQ-C30 and EORTC QLQ-H&N43 questionnaires, from enrollment to two years after treatment completion.

The clinical trial involves participants diagnosed with **Adenoid cystic carcinoma**, specifically targeting those with unresectable, locoregionally advanced, or metastatic conditions of the salivary glands. The study population includes both male and female subjects over the age of 18, with a **WHO Performance Status** ranging from 0 to 2. Participants are required to have a confirmed progression of the disease as per imaging scans following **RECIST 1.1 criteria** and must demonstrate adequate bone marrow, liver, and kidney function. The trial includes individuals who have a **68Ga-PSMA PET/CT** proven expression of PSMA, with a positive result defined as accumulation equal to or greater than that in the functional liver. The study population is selected based on these criteria, and participants must provide written informed consent. The sponsor has not provided information regarding the total number of participants. Both genders are included, and the trial considers vulnerable populations. Lifestyle considerations such as diet and physical activity are not specified, but women and men with procreative ability must agree to use a double barrier contraception method. The trial does not specify any particular lifestyle modifications or restrictions beyond these requirements.

The clinical trial is designed to evaluate the **effectiveness**, safety, and tolerability of a treatment using a specialized prostate-specific membrane antigen (PSMA) labeled with **Lutetium177** in patients with recurrent and/or metastatic **adenoid cystic carcinoma** originating from the salivary glands. This is an open, non-commercial trial, categorized as a phase 4 study. The trial employs a non-randomized, open-label design, focusing on the assessment of safety and tolerability according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). The trial is expected to run from July 1, 2023, to February 28, 2028, with an estimated duration of 36 months for each participant's involvement.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as histopathologically proven adenoid cystic carcinoma, age over 18 years, and adequate organ function. Following the screening, eligible participants will receive the investigational product, **Pluvicto 1 000 MBq/mL solution for injection/infusion**, administered via **IV infusion**. The treatment period will be monitored through regular follow-up visits to assess safety, tolerability, and treatment response. The primary endpoint is the assessment of safety and tolerability, while secondary endpoints include objective response rate, progression-free survival, overall survival, duration of response, and quality of life assessments.

The end-of-study visit will occur after the completion of the treatment period, where final assessments will be conducted. Participants are expected to remain in the study for the full duration unless conditions arise that necessitate early termination, such as significant adverse events, disease progression, or withdrawal of consent. The trial aims to provide comprehensive data on the treatment's impact on adenoid cystic carcinoma, contributing valuable insights into its potential therapeutic benefits.

The clinical trial involves the administration of **Pluvicto**, a radiopharmaceutical solution for injection/infusion, specifically formulated for the treatment of patients with recurrent and/or metastatic adenoid cystic carcinoma originating from the salivary glands. The active substance in Pluvicto is **lutetium (177Lu) vipivotide tetraxetan**, a compound classified under the ATC code V10XX, which denotes various therapeutic radiopharmaceuticals. The pharmaceutical form of Pluvicto is a solution for injection/infusion, with a concentration of 1,000 MBq/mL. The administration route is via **intravenous infusion**. The maximum daily dose is 7.4 GBq, with a total maximum dose of 44.4 GBq over a treatment period not exceeding 36 months. The product is not a pediatric formulation and is manufactured by Novartis Europharm Limited.

In this study, no non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatments are utilized. The trial's primary objective is to assess the safety and tolerability of the treatment according to the Common Terminology Criteria for Adverse Events (CTCAE v. 5.0). Participant compliance with the dosing schedule will be monitored throughout the trial to ensure adherence to the prescribed treatment regimen. The trial is open-label and non-commercial, focusing on the evaluation of the effectiveness, safety, and tolerability of the PSMA-labeled treatment with Lutetium177.

The clinical trial aims to evaluate the efficacy of a treatment using a specialized prostate-specific membrane antigen (PSMA) labeled with **Lutetium177** in patients with recurrent and/or metastatic adenoid cystic carcinoma originating from the salivary glands. Efficacy will be assessed through several secondary endpoints. These include the Objective Response Rate (ORR), which will be evaluated using CT scans according to the RECIST 1.1 criteria, two years after the completion of treatment. Progression-Free Survival (PFS) will be measured from the start of treatment to the time of disease progression or death. Overall Survival (OS) will be assessed from the start of treatment to the time of death. Duration of Response (DoR) will be evaluated from inclusion in the study to the time of progression or death in patients who achieved a complete or partial response, with this parameter assessed only in patients in remission. Additionally, the Quality of Life will be assessed using the EORTC QLQ-C30 and EORTC QLQ-H&N43 questionnaires, from enrollment in the study to two years after the completion of treatment.