<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/NCT04438824</url>
  </required_header>
  <id_info>
    <org_study_id>20-062</org_study_id>
    <secondary_id>R01FD007528-01</secondary_id>
    <nct_id>NCT04438824</nct_id>
  </id_info>
  <brief_title>Palbociclib and INCMGA00012 in People With Advanced Liposarcoma</brief_title>
  <official_title>A Phase II Study of CDK4/6 Inhibition (Palbociclib) Combined With PD-1 Blockade (INCMGA00012) in Patients With Advanced Well-differentiated Dedifferentiated Liposarcoma</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Memorial Sloan Kettering Cancer Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Incyte Corporation</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>Memorial Sloan Kettering Cancer Center</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>
      The researchers are doing this study to find out whether combining the study drugs&#xD;
      palbociclib and INCMGA00012 is an effective and safe treatment for advanced liposarcoma.&#xD;
&#xD;
      &quot;Funding Source - FDA OOPD&quot;&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">June 17, 2020</start_date>
  <completion_date type="Anticipated">June 2025</completion_date>
  <primary_completion_date type="Anticipated">June 2025</primary_completion_date>
  <phase>Phase 2</phase>
  <study_type>Interventional</study_type>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a phase II study of palbociclib plus INCMGA00012 in patients with advanced WD/DD liposarcoma.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>confirm the recommended phase two dose (RP2D</measure>
    <time_frame>within 6 weeks of treatment</time_frame>
    <description>DLTs will be assess within the first 6 weeks of the treatment combination . DLT definitions are described in section 15.4, and will be defined using NCI CTCAE v 5.0. If ≤ 1 patient out of 6 has a dose-limiting toxicity, the dosing used in the safety lead-in phase will be declared the recommended phase 2 dose. If ≥ 2 of 6 patients in the safety lead-in experience a DLT, study treatment will be halted and no further patients will be enrolled. If the study is resumed with an alternative dosing schema, a new safety lead-in phase will be completed with the new dosing regimen</description>
  </primary_outcome>
  <primary_outcome>
    <measure>best overall response rate (Phase II)</measure>
    <time_frame>by 48 weeks</time_frame>
    <description>defined by RECIST 1.1</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Safety</measure>
    <time_frame>2 years</time_frame>
    <description>Safety will be assessed using CTCAE v 5.0 to define that adverse event profile of the treatment combination and safety events will be tabulated.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>overall response rate</measure>
    <time_frame>48 weeks</time_frame>
    <description>as defined by irRECIST</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">42</enrollment>
  <condition>Well-differentiated/Dedifferentiated Liposarcoma</condition>
  <arm_group>
    <arm_group_label>Palbociclib and INCMGA00012</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Initial design (safety lead-in and expansion): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib on Day 1 and INCMGA00012 on day 15 (+/- 7 days) of each cycle at the following dose schedule: INCMGA00012: 500 mg IV (flat dose) q28 days Palbociclib: 125 mg PO daily for 21 days, followed by 7 days off, q28 days Palbociclib will be taken on Day 1 of each cycle for 21 consecutive days followed by 7 days off (days 22-28 of each Cycle). INCMGA00012 will be administered on Day 15 of (+/- 7 days) each cycle and repeat every 28 days.(No longer using this)&#xD;
Amended design (Expansion only): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib and INCMGA00012 on day 1 of each cycle: 500 mg IV (flat dose) of INCMGA00012 will be administered q28 days concurrently with palbociclib 125 mg PO daily for 21 days, followed by 7 days off, q28 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>INCMGA00012</intervention_name>
    <description>INCMGA00012: 500 mg IV (flat dose) q28 days (+/- 7 days in each cycle)</description>
    <arm_group_label>Palbociclib and INCMGA00012</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Palbociclib</intervention_name>
    <description>Palbociclib:125 mg PO daily for 21 days, followed by 7 days off, q28 days</description>
    <arm_group_label>Palbociclib and INCMGA00012</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  A diagnosis of metastatic or unresectable WD/DD liposarcoma. DD liposarcoma must be&#xD;
             present. Unresectable is defined as if the primary tumor a) cannot be safely removed&#xD;
             surgically or b) would benefit from systemic therapy prior to a surgical approach&#xD;
&#xD;
          -  Measurable disease by RECIST 1.1&#xD;
&#xD;
             a. Target lesions must not be chosen from a previously irradiated field unless there&#xD;
             has been radiographically and/or pathologically documented tumor progression in that&#xD;
             lesion prior to enrollment&#xD;
&#xD;
          -  Age ≥ 18 years&#xD;
&#xD;
          -  ECOG performance status 0 or 1&#xD;
&#xD;
          -  Adequate organ and marrow function as defined below (ULN indicates institutional upper&#xD;
             limit of normal):&#xD;
&#xD;
               1. Absolute neutrophil count ≥ 1.5 x 109/L&#xD;
&#xD;
               2. Hemoglobin ≥ 8.0 g/dL&#xD;
&#xD;
               3. WBC ≥ 3.0 x 109/L&#xD;
&#xD;
               4. Platelets ≥ 100 x 109/L&#xD;
&#xD;
               5. ≤ 1.5 X ULN OR Direct bilirubin ≤ ULN for subjects with total bilirubin levels &gt;&#xD;
                  1.5 ULN. Except patients with Gilbert's disease (≤3x ULN)&#xD;
&#xD;
               6. AST (SGOT) /ALT (SGPT) ≤ 3 x institutional ULN&#xD;
&#xD;
               7. Creatinine Clearance &gt; 30 mL/min (calculated by Cockcroft-Gault method)&#xD;
&#xD;
          -  Women of child-bearing potential and men must agree to use adequate contraception&#xD;
             (hormonal or barrier method of birth control or abstinence) during the trial period&#xD;
             through at least 120 days after the last dose of study treatment.&#xD;
&#xD;
          -  Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
          -  Ability to swallow tablets or capsules&#xD;
&#xD;
          -  Patients with brain metastasis that have been treated with definitive surgery or&#xD;
             radiation, and have been clinically stable for 3 months are eligible&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients who have not recovered from clinically significant adverse events of prior&#xD;
             therapy to ≤ NCI CTCAE v5 Grade 1, except alopecia and stable neuropathy, which must&#xD;
             have resolved to Grade ≤ 2 or baseline.&#xD;
&#xD;
          -  Patients receiving any other investigational agents.&#xD;
&#xD;
          -  Patients who have received prior treatment with a selective CDK4 inhibitor or an&#xD;
             anti-PD-1/PD-L1 agent&#xD;
&#xD;
          -  Uncontrolled intercurrent illness including, but not limited to, known ongoing or&#xD;
             active infection, including uncontrolled HIV, active hepatitis B or C, symptomatic&#xD;
             congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmias,&#xD;
             psychiatric illness/social situations that would limit compliance with study&#xD;
             requirements, clinically significant interstitial lung disease or active noninfectious&#xD;
             pneumonitis, or active infection requiring systemic therapy&#xD;
&#xD;
               1. Patients with a CD4+ count of &gt; 300 and an undetectable viral load who are&#xD;
                  currently on HAART are eligible for inclusion&#xD;
&#xD;
               2. Patients with NYHA class III or IV congestive heart failure within 6 months of&#xD;
                  study treatment will be excluded&#xD;
&#xD;
          -  Pregnant women and women who are breast-feeding.&#xD;
&#xD;
          -  History or evidence of symptomatic autoimmune disease in past 2 years prior to&#xD;
             enrollment.&#xD;
&#xD;
             a. Replacement therapy (e.g., thyroxine for hypothyroidism, insulin for diabetes or&#xD;
             physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)&#xD;
             is not considered a form of systemic treatment for autoimmune disease&#xD;
&#xD;
          -  Prolonged QTcF &gt; 450 ms for men and &gt; 470 ms for women at Screening.&#xD;
&#xD;
          -  Patients who have received a live vaccine within 30 days of the start date of the&#xD;
             planned study therapy. Note: Seasonal influenza vaccines for injection are generally&#xD;
             inactivated flu vaccines and are allowed; however intranasal influenza vaccines are&#xD;
             live attenuated vaccines, and are not allowed&#xD;
&#xD;
          -  Radiation therapy within 2 weeks prior to study Day 1&#xD;
&#xD;
          -  Prior organ transplantation including allogenic stem-cell transplantation&#xD;
&#xD;
          -  Known prior severe hypersensitivity to investigational product or any component in its&#xD;
             formulations, including known severe hypersensitivity reactions to monoclonal&#xD;
             antibodies (NCI CTCAE v 5 Grade ≥ 3)&#xD;
&#xD;
          -  Patients who require concomitant use of medications that strongly induce or inhibit&#xD;
             CYP3A (per section 15.0)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sandra D'Angelo, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Memorial Sloan Kettering Cancer Center</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Sandra D'Angelo, MD</last_name>
    <phone>646-888-4159</phone>
    <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>William Tap, MD</last_name>
    <phone>646-888-4163</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Memorial Sloan Kettering at Basking Ridge (Limited Protocol Activities)</name>
      <address>
        <city>Basking Ridge</city>
        <state>New Jersey</state>
        <zip>07920</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Monmouth (Limited Protocol Activities)</name>
      <address>
        <city>Middletown</city>
        <state>New Jersey</state>
        <zip>07748</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Bergen (Limited Protocol Activities)</name>
      <address>
        <city>Montvale</city>
        <state>New Jersey</state>
        <zip>07645</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Suffolk - Commack (Limited Protocol Activities)</name>
      <address>
        <city>Commack</city>
        <state>New York</state>
        <zip>11725</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Westchester (Limited Protocol Activities)</name>
      <address>
        <city>Harrison</city>
        <state>New York</state>
        <zip>10604</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Cancer Center</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
    <contact_backup>
      <last_name>William Tap, MD</last_name>
      <phone>646-888-4163</phone>
    </contact_backup>
  </location>
  <location>
    <facility>
      <name>Memorial Sloan Kettering Nassau (Limited protocol activities)</name>
      <address>
        <city>Rockville Centre</city>
        <state>New York</state>
        <zip>11553</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Sandra D'Angelo, MD</last_name>
      <phone>646-888-4159</phone>
      <email>zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://www.mskcc.org/mskcc/html/44.cfm</url>
    <description>Memorial Sloan Kettering Cancer Center</description>
  </link>
  <verification_date>July 2023</verification_date>
  <study_first_submitted>June 17, 2020</study_first_submitted>
  <study_first_submitted_qc>June 18, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 19, 2020</study_first_posted>
  <last_update_submitted>July 24, 2023</last_update_submitted>
  <last_update_submitted_qc>July 24, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 25, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Palbociclib</keyword>
  <keyword>INCMGA00012</keyword>
  <keyword>20-062</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Liposarcoma</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Palbociclib</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.</ipd_description>
  </patient_data>
  <!-- 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/NCT04438824
org study id: 20-062
secondary id: R01FD007528-01
nct id: NCT04438824
lead sponsor: 
collaborator: 
is fda regulated drug: Yes
is fda regulated device: No
The researchers are doing this study to find out whether combining the study drugs
      palbociclib and INCMGA00012 is an effective and safe treatment for advanced liposarcoma.

      "Funding Source - FDA OOPD"
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a phase II study of palbociclib plus INCMGA00012 in patients with advanced WD/DD liposarcoma.
primary purpose: Treatment
masking: None (Open Label)
measure: confirm the recommended phase two dose (RP2D
time frame: within 6 weeks of treatment
description: DLTs will be assess within the first 6 weeks of the treatment combination . DLT definitions are described in section 15.4, and will be defined using NCI CTCAE v 5.0. If ≤ 1 patient out of 6 has a dose-limiting toxicity, the dosing used in the safety lead-in phase will be declared the recommended phase 2 dose. If ≥ 2 of 6 patients in the safety lead-in experience a DLT, study treatment will be halted and no further patients will be enrolled. If the study is resumed with an alternative dosing schema, a new safety lead-in phase will be completed with the new dosing regimen
measure: best overall response rate (Phase II)
time frame: by 48 weeks
description: defined by RECIST 1.1
measure: Safety
time frame: 2 years
description: Safety will be assessed using CTCAE v 5.0 to define that adverse event profile of the treatment combination and safety events will be tabulated.
measure: overall response rate
time frame: 48 weeks
description: as defined by irRECIST
arm group label: Palbociclib and INCMGA00012
arm group type: Experimental
description: Initial design (safety lead-in and expansion): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib on Day 1 and INCMGA00012 on day 15 (+/- 7 days) of each cycle at the following dose schedule: INCMGA00012: 500 mg IV (flat dose) q28 days Palbociclib: 125 mg PO daily for 21 days, followed by 7 days off, q28 days Palbociclib will be taken on Day 1 of each cycle for 21 consecutive days followed by 7 days off (days 22-28 of each Cycle). INCMGA00012 will be administered on Day 15 of (+/- 7 days) each cycle and repeat every 28 days.(No longer using this)
Amended design (Expansion only): One treatment cycle will consist of 28 days. Patients in both study phases will start palbociclib and INCMGA00012 on day 1 of each cycle: 500 mg IV (flat dose) of INCMGA00012 will be administered q28 days concurrently with palbociclib 125 mg PO daily for 21 days, followed by 7 days off, q28 days.
intervention type: Drug
intervention name: INCMGA00012
description: INCMGA00012: 500 mg IV (flat dose) q28 days (+/- 7 days in each cycle)
arm group label: Palbociclib and INCMGA00012
intervention type: Drug
intervention name: Palbociclib
description: Palbociclib:125 mg PO daily for 21 days, followed by 7 days off, q28 days
arm group label: Palbociclib and INCMGA00012
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Sandra D'Angelo, MD
role: Principal Investigator
affiliation: Memorial Sloan Kettering Cancer Center
last name: Sandra D'Angelo, MD
phone: 646-888-4159
email: zzPDL_MED_Sarcoma_Clinical_Trials@mskcc.org
last name: William Tap, MD
phone: 646-888-4163
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
facility: 
status: Recruiting
contact: 
contact backup: 
facility: 
status: Recruiting
contact: 
country: United States
url: http://www.mskcc.org/mskcc/html/44.cfm
description: Memorial Sloan Kettering Cancer Center
responsible party type: Sponsor
mesh term: Liposarcoma
mesh term: Palbociclib
sharing ipd: Yes
ipd description: Memorial Sloan Kettering Cancer Center supports the international committee of medical journal editors (ICMJE) and the ethical obligation of responsible sharing of data from clinical trials. The protocol summary, a statistical summary, and informed consent form will be made available on clinicaltrials.gov when required as a condition of Federal awards, other agreements supporting the research and/or as otherwise required. Requests for deidentified individual participant data can be made beginning 12 months after publication and for up to 36 months post publication. Deidentified individual participant data reported in the manuscript will be shared under the terms of a Data Use Agreement and may only be used for approved proposals. Requests may be made to: crdatashare@mskcc.org.