<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/NCT04467515</url>
  </required_header>
  <id_info>
    <org_study_id>CAMH2_1001</org_study_id>
    <nct_id>NCT04467515</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate Safety, Tolerability, Dosimetry, and Preliminary Efficacy of the HER2 Directed Radioligand CAM-H2 in Patients With Advanced/Metastatic HER2-Positive Breast, Gastric, and Gastro-Esophageal Junction (GEJ) Cancer</brief_title>
  <official_title>A Multi-Center Open Label Dose Escalation and Dose Expansion Study to Evaluate Safety, Tolerability, Dosimetry, and Preliminary Efficacy of the HER2 Directed Radioligand CAM-H2 in Patients With Advanced/Metastatic HER2-Positive Breast, Gastric, and GEJ Cancer</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Precirix</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Precirix</source>
  <oversight_info>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to&#xD;
      evaluate safety, tolerability, dosimetry, pharmacodynamics (PD), and efficacy of the targeted&#xD;
      radionuclide therapeutic CAM-H2 in patients with progressive, advanced/metastatic&#xD;
      HER2-positive breast, gastric, and GEJ cancer with disease progression following anti-HER2&#xD;
      standard of care treatment. The study duration for each phase will be up to 18 months. The&#xD;
      study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per&#xD;
      cycle) of study drug, and a 12-month Long-Term Follow-Up Period.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 14, 2021</start_date>
  <completion_date type="Anticipated">January 17, 2025</completion_date>
  <primary_completion_date type="Anticipated">January 17, 2025</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <intervention_model_description>This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to evaluate safety, tolerability, dosimetry, PD, and efficacy of the targeted radionuclide therapeutic CAM H2 in patients with progressive, advanced/metastatic HER2 positive breast, gastric, and GEJ cancer with disease progression following anti-HER2 standard of care treatment. The study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per cycle) of study drug, and a Long Term Follow Up Period.&#xD;
The study will be comprised of the following:&#xD;
Dose Escalation Phase Followed by a Long Term Follow Up (LTFU) period&#xD;
Dose Expansion Phase Followed by a LTFU period&#xD;
In the dose expansion phase of the study, the patients will be given the recommended dose for Phase 2 (RDP2) determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Proportion of patients achieving an objective response (CR or PR) with the use of CAM-H2 as measured by the RECIST version 1.1</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Clinical benefit rate (CBR) of CAM-H2 using the equation CBR = CR + PR + SD, as measured by the RECIST version 1.1 or as measured by RANO-BM</measure>
    <time_frame>18 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Progression Free Survival (PFS) for patients receiving CAM-H2</measure>
    <time_frame>From the time of enrollment in the study to progression of disease or death, assessed up to 100 weeks)</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Duration of response (DoR) in patients receiving CAM-H2</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PFS in patients with brain metastases receiving CAM-H2</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall survival (OS) for patients receiving CAM-H2</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Proportion of patients on CAM-H2 who develop anti-drug antibodies (ADAs)</measure>
    <time_frame>18 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>Dosimetry - assessed by blood draws for blood and plasma gamma counts as well as by planar Whole body scans and SPECT/CT scans of the abdomen (kidney and liver) and of the target lesions</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Safety and Tolerability - Incidence and severity of treatment-emergent adverse events (TEAEs)</measure>
    <time_frame>18 months</time_frame>
    <description>Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0</description>
  </other_outcome>
  <other_outcome>
    <measure>Maximum tolerated dose (MTD) of CAM-H2 assessed by the number and type of DLTs as defined in the protocol that occur during the first cycle</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>Dose-limiting toxicity (DLT) rate of CAM-H2 assessed by toxicities occurring within the first cycle</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>RDP2 for CAM-H2 assessed by the number and type of DLTs as defined in the protocol that occur during the first cycle</measure>
    <time_frame>18 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">70</enrollment>
  <condition>Advanced/Metastatic HER2-positive Breast, Gastric, Gastroesophageal Junction Cancer With Disease Progression Following Anti-HER2 Standard of Care Treatment</condition>
  <arm_group>
    <arm_group_label>Dose Escalation and Expansion</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>The dose escalation phase of the study will be an open label 3 + 3 design, where at least 3 patients are treated at each dose level. Dose escalation will be done via increases of the nominal activity of CAM-H2 in cohorts of 3 to 6 patients.&#xD;
In the dose expansion phase of the study, the patients will be given the RDP2 determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>CAM-H2</intervention_name>
    <description>All patients will receive at least 1 cycle of CAM-H2. Patients with CB may receive 4 cycles of CAM-H2, each cycle given as 2 IV administrations, 4 weeks apart.</description>
    <arm_group_label>Dose Escalation and Expansion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Informed consent form signed voluntarily before any study-related procedure is&#xD;
             performed, indicating that the patient understands the purpose of, and procedures&#xD;
             required for, the study and is willing to participate in the study;&#xD;
&#xD;
          2. Males and females ≥ 18 years of age at screening;&#xD;
&#xD;
          3. Eastern Cooperative Oncology Group performance status (ECOG PS) of 0 to 1;&#xD;
&#xD;
          4. HER2-positive locally advanced or metastatic breast cancer refractory to standard&#xD;
             cancer treatment or HER2-positive locally advanced or metastatic gastric or GEJ&#xD;
             cancer, refractory to standard cancer treatment.&#xD;
&#xD;
          5. Patients should have a minimum of 1 measurable lesion as defined by RECIST version 1.1&#xD;
             or a minimum of 1 measurable lesion as defined by RANO-BM within 4 weeks of the first&#xD;
             dose of the study drug (Day 1). The lesion has to be a new lesion or progression of an&#xD;
             existing lesion under the current therapy.&#xD;
&#xD;
          6. Any previous anti-HER2 treatment for advanced or metastatic disease is allowed.&#xD;
             Patients with breast cancer should have had at least 2 previous systemic anticancer&#xD;
             treatments for recurrent, locally advanced or metastatic cancer. Patients with gastric&#xD;
             cancer or GEJ cancer should have had at least 1 previous anti-HER2 treatment.&#xD;
&#xD;
          7. Life expectancy &gt; 6 months;&#xD;
&#xD;
          8. Adequate organ function, determined by the following laboratory tests:&#xD;
&#xD;
               -  Adequate kidney function with an estimated glomerular filtration rate (eGFR) of&#xD;
                  &gt;59 mL/minute calculated using the Chronic Kidney Disease Epidemiology&#xD;
                  Collaboration equation;&#xD;
&#xD;
               -  Adequate hepatic function defined as an alanine aminotransferase (ALT) and&#xD;
                  aspartate aminotransferase (AST) &lt;2.5 x the upper limit of normal (ULN), or &lt;5 x&#xD;
                  ULN in patients with liver metastases, and total bilirubin &lt;2 x ULN;&#xD;
&#xD;
               -  Neutrophil count &gt;1500 cells/mm3 without growth factor support (14 days after&#xD;
                  last PEGylated granulocyte colony stimulating factor or 7 days after regular&#xD;
                  granulocyte colony stimulating factor);&#xD;
&#xD;
               -  Platelet count &gt;100,000 cells/mm3 without platelet transfusion in the last 2&#xD;
                  weeks;&#xD;
&#xD;
               -  Hemoglobin &gt;9.0 g/dL without blood transfusion in the last 2 weeks; and&#xD;
&#xD;
               -  Adequate coagulation defined as an international normalized ratio (INR) ≤1.5 and&#xD;
                  activated partial thromboplastin time &lt;1.5 x the upper limit of the institutional&#xD;
                  normal range;&#xD;
&#xD;
          9. Baseline left ventricular ejection fraction ≥ 50% as measured by echocardiography or&#xD;
             multigated acquisition scan.&#xD;
&#xD;
         10. Absence of any psychological, family, sociological, or geographical circumstance that&#xD;
             could potentially represent an obstacle to compliance with the study protocol and the&#xD;
             follow-up schedule, as determined by the Investigator. These circumstances will be&#xD;
             discussed with the patient before enrollment in the study; and&#xD;
&#xD;
         11. Female patients of childbearing potential (ie, ovulating, premenopausal, and not&#xD;
             surgically sterile) must have a negative pregnancy test at screening and prior to&#xD;
             study drug administration. Patients and their partners of childbearing potential must&#xD;
             be willing to use 2 methods of contraception, 1 of which must be a barrier method, for&#xD;
             the duration of the study and until 6 months after study drug administration.&#xD;
             Medically acceptable barrier methods include condom with spermicide or diaphragm with&#xD;
             spermicide. Medically acceptable non-barrier contraceptive methods include&#xD;
             intrauterine devices or hormonal contraceptives (oral, implant, injection, ring, or&#xD;
             patch).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Presence of frank leptomeningeal disease as a unique central nervous system feature or&#xD;
             in association with brain parenchymal measurable lesion(s);&#xD;
&#xD;
          2. Symptomatic brain metastases; Note: Patients with asymptomatic treated and untreated&#xD;
             brain metastases are eligible.&#xD;
&#xD;
          3. Previous local therapy for brain metastases, such as neurosurgery, stereotactic&#xD;
             radiotherapy, or whole brain radiotherapy, administered within 6 weeks prior to&#xD;
             administration of CAM-H2; Note: Previous therapy for brain metastases administered at&#xD;
             least 6 weeks prior to CAM-H2 administration will be allowed.&#xD;
&#xD;
          4. For patients with brain metastases, any increase in corticosteroid dose during the 4&#xD;
             weeks prior to the first administration of CAM-H2.&#xD;
&#xD;
             Note: Corticosteroid treatment in a stable dose or decreasing dose for at least 4&#xD;
             weeks prior to the first administration of CAM-H2 is allowed.&#xD;
&#xD;
          5. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection requiring parenteral antibiotics or psychiatric illness/social situations&#xD;
             that would limit compliance with study requirements;&#xD;
&#xD;
          6. Uncontrolled thyroid disease, defined as free triiodothyronine (T3) and free thyroxine&#xD;
             (T4) &gt; 3 x ULN at screening;&#xD;
&#xD;
          7. Uncontrolled diabetes defined as a fasting serum glucose &gt; 2 x ULN or glycated&#xD;
             hemoglobin levels &gt; 8.5% at screening;&#xD;
&#xD;
          8. Gastrointestinal (GI) tract disease resulting in an inability to take oral medication,&#xD;
             malabsorption syndrome, a requirement for intravenous (IV) alimentation, prior&#xD;
             surgical procedures affecting absorption, or uncontrolled inflammatory GI disease (eg,&#xD;
             Crohn's, ulcerative colitis);&#xD;
&#xD;
          9. Current active hepatic or biliary disease (exception of patients with Gilbert's&#xD;
             syndrome, asymptomatic gallstones, liver metastases, or stable chronic liver disease&#xD;
             per Investigator assessment);&#xD;
&#xD;
         10. Ongoing peripheral neuropathy of Grade &gt; 2 according to the Common Terminology&#xD;
             Criteria for Adverse Events (CTCAE) version 5.0;&#xD;
&#xD;
         11. Severe and/or uncontrolled medical conditions or other conditions that could affect&#xD;
             participation in the study such as:&#xD;
&#xD;
               -  Symptomatic congestive heart failure of New York Heart Association Class III or&#xD;
                  IV;&#xD;
&#xD;
               -  Unstable angina pectoris, symptomatic congestive heart failure, myocardial&#xD;
                  infarction within 6 months of start of study drug, serious uncontrolled cardiac&#xD;
                  arrhythmia, or any other clinically significant cardiac disease; or&#xD;
&#xD;
               -  Liver disease, including cirrhosis and severe hepatic impairment;&#xD;
&#xD;
         12. Active (acute or chronic) or uncontrolled severe infections;&#xD;
&#xD;
         13. Known history of HIV, hepatitis B, or active hepatitis C virus at screening;&#xD;
&#xD;
         14. Prior investigational anticancer therapy within 4 weeks prior to the first&#xD;
             administration of CAM-H2.&#xD;
&#xD;
         15. Patients who have had a major surgery or significant traumatic injury within 4 weeks&#xD;
             prior to the first administration of CAM-H2, who have not recovered from side effects&#xD;
             of any major surgery (defined as requiring general anesthesia), or have a major&#xD;
             surgery planned during the course of the study;&#xD;
&#xD;
         16. Other malignancies within the past 3 years except for adequately treated carcinoma of&#xD;
             the cervix or basal or squamous cell carcinomas of the skin or stage I uterine cancer;&#xD;
&#xD;
         17. Radiation therapy for metastatic disease foci outside the brain, administered within 3&#xD;
             weeks prior to the first administration of CAM-H2;&#xD;
&#xD;
         18. Known hypersensitivity to any of the study drugs (including inactive ingredients),&#xD;
             including iodine allergy;&#xD;
&#xD;
         19. History of significant comorbidities that, in the Investigator's judgement, may&#xD;
             interfere with study conduct, response assessment, or informed consent;&#xD;
&#xD;
         20. Unable or unwilling to complete the study procedures;&#xD;
&#xD;
         21. Patients that cannot be hospitalized in a radionuclide therapy room;&#xD;
&#xD;
         22. Patients with urinary incontinence;&#xD;
&#xD;
         23. Patients that are unable to comply with thyroid protective pre-medication;&#xD;
&#xD;
         24. Patients in whom bladder catheterization cannot be performed, or in patients who are&#xD;
             unwilling to be catheterized if necessary;&#xD;
&#xD;
         25. Patients with contraindications for undergoing MRI or computed tomography (CT),&#xD;
             including for receiving contrast agents; or&#xD;
&#xD;
         26. Patient is the Investigator or sub-Investigator, research assistant, pharmacist, study&#xD;
             coordinator, or other staff or relative thereof, who is directly involved in the&#xD;
             conduct of the study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>City of Hope</name>
      <address>
        <city>Duarte</city>
        <state>California</state>
        <zip>91010</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Jeffrey Wong</last_name>
      <phone>626-218-3533</phone>
      <email>JWong@coh.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Carina Mari Aparici</last_name>
      <phone>650-736-4183</phone>
      <email>drmari@stanford.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Georgetown University Medical Center</name>
      <address>
        <city>Washington</city>
        <state>District of Columbia</state>
        <zip>20057</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Giuseppe Esposito</last_name>
      <phone>202-713-8849</phone>
      <email>EXG11@gunet.georgetown.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Loyola University Medical Center</name>
      <address>
        <city>Maywood</city>
        <state>Illinois</state>
        <zip>60153</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Robert Wagner</last_name>
      <email>RWAGNER@lumc.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Kristin Plichta</last_name>
      <phone>319-384-6469</phone>
      <email>kristin-plichta@uiowa.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>University of Kentucky</name>
      <address>
        <city>Lexington</city>
        <state>Kentucky</state>
        <zip>40536</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Withdrawn</status>
  </location>
  <location>
    <facility>
      <name>Johns Hopkins Hospital</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21287</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Martin Pomper</last_name>
      <phone>443-287-1622</phone>
      <email>mpomper@jhmi.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Advanced Molecular Imaging &amp; Therapy</name>
      <address>
        <city>Glen Burnie</city>
        <state>Maryland</state>
        <zip>21061</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Michael Morris</last_name>
      <phone>443-333-1894</phone>
      <email>morrism@amit.health</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Washington University School of Medicine in St. Louis</name>
      <address>
        <city>Saint Louis</city>
        <state>Missouri</state>
        <zip>63110</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Richard Wahl</last_name>
      <email>rwahl@wustl.edu</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>David H. Koch Center for Cancer Care at Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10021</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Not yet recruiting</status>
    <contact>
      <last_name>Lisa Bodei</last_name>
      <phone>212-639-8146</phone>
      <email>bodeil@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Princess Margaret Hospital</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Rebecca Wong</last_name>
      <phone>416 946 2983</phone>
      <email>Rebecca.Wong@rmp.uhn.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Hospital Notre Dame du CHUM</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>David Roberge</last_name>
      <phone>514 890 8254</phone>
      <email>david.roberge.chum@ssss.gouv.qc.ca</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>McGill University Faculty of Medicine - Royal Victoria Hospital</name>
      <address>
        <city>Montréal</city>
        <state>Quebec</state>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Catalin Mihalcioiu</last_name>
      <phone>514 934 1934</phone>
      <email>catalin.mihalcioiu@muhc.mcgill.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2023</verification_date>
  <study_first_submitted>June 10, 2020</study_first_submitted>
  <study_first_submitted_qc>July 7, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 13, 2020</study_first_posted>
  <last_update_submitted>January 5, 2023</last_update_submitted>
  <last_update_submitted_qc>January 5, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">January 6, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Disease Progression</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


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/NCT04467515
org study id: CAMH2_1001
nct id: NCT04467515
lead sponsor: 
is fda regulated drug: Yes
is fda regulated device: No
This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to
      evaluate safety, tolerability, dosimetry, pharmacodynamics (PD), and efficacy of the targeted
      radionuclide therapeutic CAM-H2 in patients with progressive, advanced/metastatic
      HER2-positive breast, gastric, and GEJ cancer with disease progression following anti-HER2
      standard of care treatment. The study duration for each phase will be up to 18 months. The
      study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per
      cycle) of study drug, and a 12-month Long-Term Follow-Up Period.
allocation: N/A
intervention model: Sequential Assignment
intervention model description: This is a Phase 1/2 multi-center, open label, dose escalation and dose expansion study to evaluate safety, tolerability, dosimetry, PD, and efficacy of the targeted radionuclide therapeutic CAM H2 in patients with progressive, advanced/metastatic HER2 positive breast, gastric, and GEJ cancer with disease progression following anti-HER2 standard of care treatment. The study is comprised of a Treatment Period, consisting of a maximum of 4 cycles (12 weeks per cycle) of study drug, and a Long Term Follow Up Period.
The study will be comprised of the following:
Dose Escalation Phase Followed by a Long Term Follow Up (LTFU) period
Dose Expansion Phase Followed by a LTFU period
In the dose expansion phase of the study, the patients will be given the recommended dose for Phase 2 (RDP2) determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.
primary purpose: Treatment
masking: None (Open Label)
measure: Proportion of patients achieving an objective response (CR or PR) with the use of CAM-H2 as measured by the RECIST version 1.1
time frame: 18 months
measure: Clinical benefit rate (CBR) of CAM-H2 using the equation CBR = CR + PR + SD, as measured by the RECIST version 1.1 or as measured by RANO-BM
time frame: 18 months
measure: Progression Free Survival (PFS) for patients receiving CAM-H2
time frame: From the time of enrollment in the study to progression of disease or death, assessed up to 100 weeks)
measure: Duration of response (DoR) in patients receiving CAM-H2
time frame: 18 months
measure: PFS in patients with brain metastases receiving CAM-H2
time frame: 18 months
measure: Overall survival (OS) for patients receiving CAM-H2
time frame: 18 months
measure: Proportion of patients on CAM-H2 who develop anti-drug antibodies (ADAs)
time frame: 18 months
measure: Dosimetry - assessed by blood draws for blood and plasma gamma counts as well as by planar Whole body scans and SPECT/CT scans of the abdomen (kidney and liver) and of the target lesions
time frame: 18 months
measure: Safety and Tolerability - Incidence and severity of treatment-emergent adverse events (TEAEs)
time frame: 18 months
description: Assessed by the Common Terminology Criteria for Adverse Events (CTCAE) version 5.0
measure: Maximum tolerated dose (MTD) of CAM-H2 assessed by the number and type of DLTs as defined in the protocol that occur during the first cycle
time frame: 18 months
measure: Dose-limiting toxicity (DLT) rate of CAM-H2 assessed by toxicities occurring within the first cycle
time frame: 18 months
measure: RDP2 for CAM-H2 assessed by the number and type of DLTs as defined in the protocol that occur during the first cycle
time frame: 18 months
arm group label: Dose Escalation and Expansion
arm group type: Experimental
description: The dose escalation phase of the study will be an open label 3 + 3 design, where at least 3 patients are treated at each dose level. Dose escalation will be done via increases of the nominal activity of CAM-H2 in cohorts of 3 to 6 patients.
In the dose expansion phase of the study, the patients will be given the RDP2 determined in the dose escalation phase. Similar to the dose escalation phase, all patients will receive at least 1 cycle of CAM-H2.
intervention type: Drug
intervention name: CAM-H2
description: All patients will receive at least 1 cycle of CAM-H2. Patients with CB may receive 4 cycles of CAM-H2, each cycle given as 2 IV administrations, 4 weeks apart.
arm group label: Dose Escalation and Expansion
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Withdrawn
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Not yet recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
country: Canada
country: United States
responsible party type: Sponsor
mesh term: Disease Progression