xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05983198</url>
    </required_header>
    <id_info>
      <org_study_id>CAAA802A12101</org_study_id>
      <secondary_id>2021-003478-30</secondary_id>
      <nct_id>NCT05983198</nct_id>
    </id_info>
    <brief_title>A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With PSMA-positive Prostate Cancer With or Without Prior 177Lu-PSMA Radioligand Therapy.</brief_title>
    <official_title>SatisfACtion: A Phase I/II, Open-label, Multi-center Study of [225Ac]Ac-PSMA-R2 in Men With Heavily Pre-treated PSMA Positive Metastatic Castration Resistant Prostate Cancer (mCRPC) With or Without Prior 177Lu-labelled PSMA-targeted Radioligand Therapy.</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Novartis Pharmaceuticals</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>Novartis</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
      <is_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The purpose of the study is to characterize the safety, tolerability, pharmacokinetics (PK),&#xD;
        and anti-tumor activity of 225Ac-PSMA-R2 in male adult participants with metastatic&#xD;
        castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor&#xD;
        pathway inhibitors in post-177Lu and pre-177Lu settings.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        This is an open label, phase I/II, multi-center study which contains two treatment groups&#xD;
        (Group 1 and Group 2). Each group has a dose escalation part, once the Maximum Tolerated&#xD;
        Dose/Recommended Dose for Expansion (MTD/RDE) is determined in each of the dose escalation&#xD;
        parts, the study will continue with an expansion part in the respective group.&#xD;
  &#xD;
        The dose escalation parts will establish the MTD/RDE of the 225Ac-PSMA-R2 guided by the&#xD;
        well-established Bayesian Logistic Regression Model (BLRM) method. The adaptive BLRM will be&#xD;
        guided by the Escalation with Overdose Control (EWOC) principle to control the risk of DLT in&#xD;
        future participants on study. Dose escalation decisions will be performed by the&#xD;
        Investigators and Novartis during dose escalation meetings (DEMs) based on safety and&#xD;
        tolerability information (BLRM summaries of DLT risk) along with PK and preliminary efficacy&#xD;
        information.&#xD;
  &#xD;
        The dose expansion parts will assess the anti-tumor activity (Overall Response Rate (ORR) by&#xD;
        Prostate Cancer Working Group 3 (PCWG3) modified RECIST 1.1 and Prostate Specific Antigen 50&#xD;
        (PSA50) response rate) as well as further assess the safety, tolerability, and PK of&#xD;
        225Ac-PSMA-R2.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 29, 2023</start_date>
    <completion_date type="Anticipated">August 28, 2026</completion_date>
    <primary_completion_date type="Anticipated">August 28, 2026</primary_completion_date>
    <phase>Phase 1/Phase 2</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Treatment</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Dose Escalation: Incidence and severity of Dose Limiting Toxicity (DLTs) during the first cycle of treatment</measure>
      <time_frame>Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration</time_frame>
      <description>To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive mCRPC in:&#xD;
  Group-1: Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu).&#xD;
  Group-2: Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs) during the first cycle of treatment.</measure>
      <time_frame>Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration</time_frame>
      <description>The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Expansion: Overall Response Rate (ORR)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue, as per BICR and according to Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, in the absence of bone progression as per PCWG3. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Dose Expansion: Percentage of participants achieving prostate-specific antigen (PSA) response 50 (PSA50)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months</time_frame>
      <description>PSA50 response rate is defined as the proportion of participants who have achieved &gt;= 50% decrease in PSA from baseline confirmed by a second PSA measurement &gt;= 4 weeks.</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)</measure>
      <time_frame>Up to 6 months after the last 225Ac-PSMA-R2 dose administration</time_frame>
      <description>The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months</time_frame>
      <description>The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.</measure>
      <time_frame>Cycles 1 to 6 (1 cycle = 6 weeks)</time_frame>
      <description>Tolerability of study drug will be assessed by summarizing the number of and the reasons for dose delays and dose reductions. Dose intensity will also be tabulated by treatment group.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Overall Response Rate (ORR)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue, as per BICR and according to Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, in the absence of bone progression as per PCWG3. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Disease Control Rate (DCR)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Disease control rate (DCR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD), as per central and local review and according to PCWG3-modified RECIST v1.1.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Best Overall Response (BOR)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Best Overall Response (BOR) is defined to derive Overall Response Rate (ORR) and includes complete response (CR) or partial response (PR). BOR is determined from the sequence of overall responses.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: radiographic Progression Free Survival (rPFS)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Radiographic progression free survival (rPFS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of radiographic progression as outlined in PCWG3 guideline or death due to any cause.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Overall Survival (OS)</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 until date of death from any cause, assessed up to approximately 15 months</time_frame>
      <description>Overall survival (OS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Duration of Response (DoR)</measure>
      <time_frame>From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to approximately 15 months</time_frame>
      <description>Duration of response (DOR) is defined as the time (in months) from the date of the first documented response (CR or PR) to the date of first documented progression according to PCWG3-modified RECIST v1.1 or death due to any cause, among participants with a confirmed response.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Time to first Symptomatic Skeletal Event (SSE)</measure>
      <time_frame>From the date of the first administration of 225Ac-PSMA-R2 until the date of SSE or date of death from any cause, whichever comes first, assessed up to approximately 15 months</time_frame>
      <description>Time to a first symptomatic skeletal event (SSE) is defined as the time (in months) from the first administration of 225Ac-PSMA-R2 to the date of SSE or death due to any cause. SSE date is date of the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever comes first.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation &amp; Dose Expansion: Percentage of Participants with Biochemical Response</measure>
      <time_frame>From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months</time_frame>
      <description>Biochemical responses as measured by Prostate Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH).</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Area under the serum concentration-time cure from time zero to the time of last quantifiable concentration (AUClast) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Maximum plasma concentration (Cmax) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Total systemic clearance for intravenous administration (CL) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Time of observed drug concentration occurrence (Tmax) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Escalation: Terminal elimination half-life (T1/2) of 225Ac-PSMA-R2 during the first cycle of treatment</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T1/2 will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Area under the serum concentration-time cure from time zero to the time of last quantifiable concentration (AUClast) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Maximum plasma concentration (Cmax) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Total systemic clearance for intravenous administration (CL) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Time of observed drug concentration occurrence (Tmax) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Dose Expansion: Terminal elimination half-life (T1/2) of 225Ac-PSMA-R2</measure>
      <time_frame>Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks</time_frame>
      <description>Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T1/2 will be listed and summarized using descriptive statistics.</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Metastatic Castration-resistant Prostate Cancer (mCRPC)</condition>
    <arm_group>
      <arm_group_label>Group-1 (post-177Lu)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose Escalation: All eligible participants with mCRPC heavily pre-treated and refractory to 177Lu-labelled PSMA-targeting RLT will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1.&#xD;
  Dose Expansion: Once RDE is determined for Group-1, participants being non/partial responders to 177Lu-labelled PSMA-targeted RLT or requiring re-treatment/re-challenge after 177Lu-labelled PSMA-targeted RLT treatment will be enrolled in Group 1 dose expansion.</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Group-2 (pre-177Lu)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>Dose Escalation: All eligible participants with mCRPC who have received previous treatment with Androgen Receptor Pathway Inhibitors (ARPI) or Computed Tomography (CT) but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive one level higher than the RDE of Group 1 as the starting dose of 225Ac-PSMA-R2 in order to determine the MTD/RDE of Group 2.&#xD;
  Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted RLT with high volume soft tissue and visceral disease and in participants with diffuse bone metastasis will be enrolled in Group 2 dose expansion.&#xD;
  Alternatively, if the RDE1 is not determined, Group 2 will begin the evaluation for the dose escalation at the dose of 7 MBq of 225Ac-PSMA-R2 upon Novartis decision. The early starting of Group 2 will be supported by emerging safety and preliminary efficacy data from Group 1 dose escalation.</description>
    </arm_group>
    <intervention>
      <intervention_type>Drug</intervention_type>
      <intervention_name>225Ac-PSMA-R2</intervention_name>
      <description>PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide</description>
      <arm_group_label>Group-1 (post-177Lu)</arm_group_label>
      <arm_group_label>Group-2 (pre-177Lu)</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Radiation</intervention_type>
      <intervention_name>68Ga-PSMA-R2</intervention_name>
      <description>Kit for radiopharmaceutical preparation</description>
      <arm_group_label>Group-1 (post-177Lu)</arm_group_label>
      <arm_group_label>Group-2 (pre-177Lu)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Key Inclusion Criteria:&#xD;
  &#xD;
            -  Evidence of PSMA-positive disease by 68Ga-PSMA-R2 PET/CT and eligible as determined by&#xD;
               central reading&#xD;
  &#xD;
            -  Documented progressive mCRPC&#xD;
  &#xD;
            -  Adequate organ function (bone marrow reserve, hepatic, renal)&#xD;
  &#xD;
            -  Prior orchiectomy and/or ongoing ARPI and taxane-based chemotherapy and should have&#xD;
               received prior 177Lu-PSMA-RLT (Group1 dose escalation &amp; expansion) or never received&#xD;
               177Lu-PSMA-RLT (Group 2 dose escalation &amp; expansion).&#xD;
  &#xD;
          Key Exclusion Criteria:&#xD;
  &#xD;
            -  Any other investigational agents within 28 days of the anticipated C1D1 of&#xD;
               225Ac-PSMA-R2 therapy&#xD;
  &#xD;
            -  Any systemic anti-cancer therapy within 28 days of the anticipated C1D1 of&#xD;
               225Ac-PSMA-R2 therapy&#xD;
  &#xD;
            -  Uncontrolled pain or incompatibility that may result in participant's lack of ability&#xD;
               to comply with imaging procedures&#xD;
  &#xD;
            -  History of CNS metastases and symptomatic cord compression, or clinical or radiologic&#xD;
               findings indicative of impending cord compression&#xD;
  &#xD;
            -  Uncontrolled cardiovascular history&#xD;
  &#xD;
            -  Diagnosis of other malignancies expected to alter life expectancy or may interfere&#xD;
               with disease assessment&#xD;
  &#xD;
          Other protocol-defined inclusion/exclusion criteria may apply.&#xD;
        </textblock>
      </criteria>
      <gender>Male</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Novartis Pharmaceuticals</last_name>
      <role>Study Director</role>
      <affiliation>Novartis Pharmaceuticals</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Novartis Pharmaceuticals</last_name>
      <phone>+41613241111</phone>
      <email>novartis.email@novartis.com</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Novartis Pharmaceuticals</last_name>
    </overall_contact_backup>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 24, 2023</study_first_submitted>
    <study_first_submitted_qc>August 8, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 9, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>225Ac-PSMA-R2</keyword>
    <keyword>dose limiting toxicity</keyword>
    <keyword>DLT</keyword>
    <keyword>Escalation with Overdose Control</keyword>
    <keyword>EWOC</keyword>
    <keyword>pre- and post-177Lu-PSMA-RLT</keyword>
    <keyword>pre- and post-177Lu-PSMA-617</keyword>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Prostatic Neoplasms</mesh_term>
    </condition_browse>
    <intervention_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Gallium 68 PSMA-11</mesh_term>
    </intervention_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05983198
  org study id: CAAA802A12101
  secondary id: 2021-003478-30
  nct id: NCT05983198
  lead sponsor: 
  has dmc: No
  is fda regulated drug: Yes
  is fda regulated device: No
  is us export: No
  The purpose of the study is to characterize the safety, tolerability, pharmacokinetics (PK),
        and anti-tumor activity of 225Ac-PSMA-R2 in male adult participants with metastatic
        castration-resistant prostate cancer (mCRPC) previously treated with androgen receptor
        pathway inhibitors in post-177Lu and pre-177Lu settings.
  This is an open label, phase I/II, multi-center study which contains two treatment groups
        (Group 1 and Group 2). Each group has a dose escalation part, once the Maximum Tolerated
        Dose/Recommended Dose for Expansion (MTD/RDE) is determined in each of the dose escalation
        parts, the study will continue with an expansion part in the respective group.
  
        The dose escalation parts will establish the MTD/RDE of the 225Ac-PSMA-R2 guided by the
        well-established Bayesian Logistic Regression Model (BLRM) method. The adaptive BLRM will be
        guided by the Escalation with Overdose Control (EWOC) principle to control the risk of DLT in
        future participants on study. Dose escalation decisions will be performed by the
        Investigators and Novartis during dose escalation meetings (DEMs) based on safety and
        tolerability information (BLRM summaries of DLT risk) along with PK and preliminary efficacy
        information.
  
        The dose expansion parts will assess the anti-tumor activity (Overall Response Rate (ORR) by
        Prostate Cancer Working Group 3 (PCWG3) modified RECIST 1.1 and Prostate Specific Antigen 50
        (PSA50) response rate) as well as further assess the safety, tolerability, and PK of
        225Ac-PSMA-R2.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Treatment
  masking: None (Open Label)
  measure: Dose Escalation: Incidence and severity of Dose Limiting Toxicity (DLTs) during the first cycle of treatment
  time frame: Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration
  description: To determine the Recommended Dose for Expansion (RDE) and corresponding regimen for 225Ac-PSMA-R2 monotherapy in PSMA-positive mCRPC in:
  Group-1: Participants previously treated with 177Lu-labelled PSMA-targeted RLT (post-177Lu).
  Group-2: Participants not treated previously with 177Lu-labelled PSMA-targeted RLT (pre-177Lu).
  measure: Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs) during the first cycle of treatment.
  time frame: Up to 6 weeks after the first 225Ac-PSMA-R2 dose administration
  description: The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
  measure: Dose Expansion: Overall Response Rate (ORR)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue, as per BICR and according to Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, in the absence of bone progression as per PCWG3. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.
  measure: Dose Expansion: Percentage of participants achieving prostate-specific antigen (PSA) response 50 (PSA50)
  time frame: From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
  description: PSA50 response rate is defined as the proportion of participants who have achieved >= 50% decrease in PSA from baseline confirmed by a second PSA measurement >= 4 weeks.
  measure: Dose Escalation: Incidence and severity of AEs and serious adverse events (SAEs)
  time frame: Up to 6 months after the last 225Ac-PSMA-R2 dose administration
  description: The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
  measure: Dose Expansion: Incidence and severity of AEs and serious adverse events (SAEs)
  time frame: From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
  description: The distribution of adverse events will be done via the analysis of frequencies for treatment emergent Adverse Event (TEAEs), Serious Adverse Event (TESAEs) and Deaths due to AEs, through the monitoring of relevant clinical and laboratory safety parameters.
  measure: Dose Escalation & Dose Expansion: Frequency of dose interruptions, reductions, discontinuations, and dose intensity by treatment.
  time frame: Cycles 1 to 6 (1 cycle = 6 weeks)
  description: Tolerability of study drug will be assessed by summarizing the number of and the reasons for dose delays and dose reductions. Dose intensity will also be tabulated by treatment group.
  measure: Dose Escalation: Overall Response Rate (ORR)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Overall Response Rate (ORR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR) or partial response (PR) in soft tissue, as per BICR and according to Prostate Cancer Working Group 3 (PCWG3)-modified RECIST v1.1, in the absence of bone progression as per PCWG3. CR and PR must be confirmed by repeat assessments that should be performed not less than 4 weeks after the criteria for response are first met.
  measure: Dose Escalation & Dose Expansion: Disease Control Rate (DCR)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Disease control rate (DCR) is defined as the proportion of participants with best overall response (BOR) of complete response (CR), partial response (PR) or stable disease (SD), as per central and local review and according to PCWG3-modified RECIST v1.1.
  measure: Dose Escalation & Dose Expansion: Best Overall Response (BOR)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Best Overall Response (BOR) is defined to derive Overall Response Rate (ORR) and includes complete response (CR) or partial response (PR). BOR is determined from the sequence of overall responses.
  measure: Dose Escalation & Dose Expansion: radiographic Progression Free Survival (rPFS)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of radiographic progression or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Radiographic progression free survival (rPFS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of radiographic progression as outlined in PCWG3 guideline or death due to any cause.
  measure: Dose Escalation & Dose Expansion: Overall Survival (OS)
  time frame: From date of the first administration of 225Ac-PSMA-R2 until date of death from any cause, assessed up to approximately 15 months
  description: Overall survival (OS) is defined as the time (in months) from the date of the first administration of 225Ac-PSMA-R2 to the date of death due to any cause. If a participant is not known to have died, then OS will be censored at the latest date the participant was known to be alive (on or before the cut-off date).
  measure: Dose Escalation & Dose Expansion: Duration of Response (DoR)
  time frame: From the date of the first documented response (CR or PR) to the date of first documented progression or death due to any cause, assessed up to approximately 15 months
  description: Duration of response (DOR) is defined as the time (in months) from the date of the first documented response (CR or PR) to the date of first documented progression according to PCWG3-modified RECIST v1.1 or death due to any cause, among participants with a confirmed response.
  measure: Dose Escalation & Dose Expansion: Time to first Symptomatic Skeletal Event (SSE)
  time frame: From the date of the first administration of 225Ac-PSMA-R2 until the date of SSE or date of death from any cause, whichever comes first, assessed up to approximately 15 months
  description: Time to a first symptomatic skeletal event (SSE) is defined as the time (in months) from the first administration of 225Ac-PSMA-R2 to the date of SSE or death due to any cause. SSE date is date of the first new symptomatic pathological bone fracture, spinal cord compression, tumor-related orthopedic surgical intervention, requirement for radiation therapy to relieve bone pain, or death due to any cause, whichever comes first.
  measure: Dose Escalation & Dose Expansion: Percentage of Participants with Biochemical Response
  time frame: From date of the first administration of 225Ac-PSMA-R2 till 30 days safety follow-up, assessed up to approximately 15 months
  description: Biochemical responses as measured by Prostate Specific Antigen (PSA), Alkaline Phosphatase (ALP), Lactate Dehydrogenase (LDH).
  measure: Dose Escalation: Area under the serum concentration-time cure from time zero to the time of last quantifiable concentration (AUClast) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Maximum plasma concentration (Cmax) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Total systemic clearance for intravenous administration (CL) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Time of observed drug concentration occurrence (Tmax) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
  measure: Dose Escalation: Terminal elimination half-life (T1/2) of 225Ac-PSMA-R2 during the first cycle of treatment
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T1/2 will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Area under the serum concentration-time cure from time zero to the time of last quantifiable concentration (AUClast) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUClast will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Area under the plasma concentration-time curve from time zero to infinity (AUCinf) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. AUCinf will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Maximum plasma concentration (Cmax) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Cmax will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Total systemic clearance for intravenous administration (CL) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. CL will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Time of observed drug concentration occurrence (Tmax) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Tmax will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Volume of distribution during the terminal phase following intravenous elimination (Vz) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. Vz will be listed and summarized using descriptive statistics.
  measure: Dose Expansion: Terminal elimination half-life (T1/2) of 225Ac-PSMA-R2
  time frame: Cycle (C) 1 Day (D) 1 (Pre-dose (before start of infusion), Mid-infusion, Just before or at the end of infusion, Post-dose (5 minutes (min), 15 min, 30 min, 1 hour (hr), 2 hr, 4 hr, 8 hr)), C1 D2 (24 hr), C1 D3 (48 hr), C1 D4 (72 hr). Cycle = 6 weeks
  description: Venous whole blood samples will be collected for activity-based pharmacokinetics characterization. T1/2 will be listed and summarized using descriptive statistics.
  arm group label: Group-1 (post-177Lu)
  arm group type: Experimental
  description: Dose Escalation: All eligible participants with mCRPC heavily pre-treated and refractory to 177Lu-labelled PSMA-targeting RLT will receive the starting dose of 7 Megabecquerel (MBq) of 225Ac-PSMA-R2 to determine the Maximum Tolerated Dose/Recommended Dose for Expansion (MTD/RDE) of Group 1.
  Dose Expansion: Once RDE is determined for Group-1, participants being non/partial responders to 177Lu-labelled PSMA-targeted RLT or requiring re-treatment/re-challenge after 177Lu-labelled PSMA-targeted RLT treatment will be enrolled in Group 1 dose expansion.
  arm group label: Group-2 (pre-177Lu)
  arm group type: Experimental
  description: Dose Escalation: All eligible participants with mCRPC who have received previous treatment with Androgen Receptor Pathway Inhibitors (ARPI) or Computed Tomography (CT) but have never been treated with 177Lu-labelled PSMA-targeted RLT (177Lu-labelled PSMA-targeted RLT treatment naïve) will receive one level higher than the RDE of Group 1 as the starting dose of 225Ac-PSMA-R2 in order to determine the MTD/RDE of Group 2.
  Dose Expansion: Once RDE is determined for Group 2, participants naïve to 177Lu-labelled PSMA-targeted RLT with high volume soft tissue and visceral disease and in participants with diffuse bone metastasis will be enrolled in Group 2 dose expansion.
  Alternatively, if the RDE1 is not determined, Group 2 will begin the evaluation for the dose escalation at the dose of 7 MBq of 225Ac-PSMA-R2 upon Novartis decision. The early starting of Group 2 will be supported by emerging safety and preliminary efficacy data from Group 1 dose escalation.
  intervention type: Drug
  intervention name: 225Ac-PSMA-R2
  description: PSMA-R2 is a ligand coupled with 225Ac an alpha emitting radionuclide
  arm group label: Group-1 (post-177Lu)
  arm group label: Group-2 (pre-177Lu)
  intervention type: Radiation
  intervention name: 68Ga-PSMA-R2
  description: Kit for radiopharmaceutical preparation
  arm group label: Group-1 (post-177Lu)
  arm group label: Group-2 (pre-177Lu)
  criteria: 
  gender: Male
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Novartis Pharmaceuticals
  role: Study Director
  affiliation: Novartis Pharmaceuticals
  last name: Novartis Pharmaceuticals
  phone: +41613241111
  email: novartis.email@novartis.com
  last name: Novartis Pharmaceuticals
  responsible party type: Sponsor
  mesh term: Prostatic Neoplasms
  mesh term: Gallium 68 PSMA-11
  sharing ipd: No