<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/NCT03784040</url>
  </required_header>
  <id_info>
    <org_study_id>GA01/03/18</org_study_id>
    <secondary_id>2018/00422</secondary_id>
    <nct_id>NCT03784040</nct_id>
  </id_info>
  <brief_title>Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.</brief_title>
  <acronym>da VINci</acronym>
  <official_title>da VINci Study (OTSGC-A24 Therapeutic Peptide Vaccine + Ipilimumab + Nivolumab) Nivolumab, Ipilimumab and OTSGC-A24 Therapeutic Peptide Vaccine in Gastric Cancer - a Combination Immunotherapy Phase Ib Study.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National University Hospital, Singapore</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>OncoTherapy Science, Inc.</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
    <collaborator>
      <agency>Bristol-Myers Squibb</agency>
      <agency_class>Industry</agency_class>
    </collaborator>
  </sponsors>
  <source>National University Hospital, Singapore</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary hypothesis is that cancer vaccine can convert non-immunogenic gastric cancer into&#xD;
      immunogenic phenotype susceptible to PD1 inhibition. This would lead to an improved&#xD;
      radiological response rate and favorable immune contexture for immune checkpoint blockade&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Primary Objectives&#xD;
&#xD;
        1. Safety cohorts: To evaluate the safety of OTSGC-A24 and nivolumab (+ ipilimumab) in&#xD;
           patients with refractory gastric cancer.&#xD;
&#xD;
        2. Arm A: To determine the objective response rate of OTSGC-A24 and nivolumab in advanced&#xD;
           gastric cancer.&#xD;
&#xD;
        3. Arm B: To determine the objective response rate of OTSGC-A24 and nivolumab + ipilimumab&#xD;
           in advanced gastric cancer.&#xD;
&#xD;
      Secondary Objectives&#xD;
&#xD;
        1. To compare the difference in objective response rates between Arm A and Arm B&#xD;
&#xD;
        2. To compare the tumoral immune contexture and PDL-1 expression before treatment, after&#xD;
           OTSGC-A24, and after nivolumab (+ ipilimumab) in combination with OTSGC-A24.&#xD;
&#xD;
        3. To determine the serum cytotoxic T-cell response using enzyme-linked immunospot assay&#xD;
           (ELISPOT) in PBMC.&#xD;
&#xD;
        4. To determine the progression-free survival (PFS) and overall survival (OS) of Arm A and&#xD;
           Arm B.&#xD;
&#xD;
        5. To evaluate the effect of OTSGC-A24 and nivolumab + ipilimumab on clinical and immune PD&#xD;
           markers.&#xD;
&#xD;
        6. Evaluate the effects of treatment on peripheral T-cell phenotypic profiles with&#xD;
           epitope-specificities by coupling mass cytometric analyses with highly-multiplexed&#xD;
           peptide-MHC tetramer staining technology.&#xD;
&#xD;
        7. Identify potential biomarkers for treatment response and mechanisms of secondary&#xD;
           resistance by studying gene expression profiles and phenotypic/functional markers of&#xD;
           tumour and infiltrating immune cells.&#xD;
&#xD;
      End Points - Efficacy&#xD;
&#xD;
      The endpoints for efficacy are:&#xD;
&#xD;
        -  Induction of specific CTL response after vaccination&#xD;
&#xD;
        -  Response rate&#xD;
&#xD;
        -  Progression-free survival&#xD;
&#xD;
        -  Overall survival End Points - Safety&#xD;
&#xD;
      The endpoints for safety are:&#xD;
&#xD;
      • overall adverse events observed, treatment-related adverse events, and category (eg&#xD;
      percentage of patients with any-grade treatment-related adverse events and grade 3-4&#xD;
      treatment-related adverse events).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">February 21, 2019</start_date>
  <completion_date type="Anticipated">March 1, 2024</completion_date>
  <primary_completion_date type="Anticipated">March 1, 2023</primary_completion_date>
  <phase>Phase 1</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>Adverse Event and Adverse Drug Reaction</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <primary_outcome>
    <measure>Response Rate</measure>
    <time_frame>3 years</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Rate of induction of specific CTL response</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Progression-free Survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Overall Survival</measure>
    <time_frame>3 years</time_frame>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Gastric Cancer</condition>
  <arm_group>
    <arm_group_label>(Arm A) OTSGC-A24 + nivolumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14 each 28 day cycle (q28d) for up to 24 months.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>(Arm B) OTSGC-A24 + nivolumab + ipilimumab</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14. Ipilimumab 1mg/kg (IV) will be administered q6w (i.e. C1D1, C2D15, C3D1 …) of each 28 day cycle for up to 24 months.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>OTSGC-A24</intervention_name>
    <description>OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.</description>
    <arm_group_label>(Arm A) OTSGC-A24 + nivolumab</arm_group_label>
    <arm_group_label>(Arm B) OTSGC-A24 + nivolumab + ipilimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Nivolumab</intervention_name>
    <description>OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.</description>
    <arm_group_label>(Arm A) OTSGC-A24 + nivolumab</arm_group_label>
    <arm_group_label>(Arm B) OTSGC-A24 + nivolumab + ipilimumab</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Ipilimumab</intervention_name>
    <description>OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.</description>
    <arm_group_label>(Arm B) OTSGC-A24 + nivolumab + ipilimumab</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Histologically or cytologically confirmed inoperable or metastatic gastric cancer that&#xD;
             has failed or demonstrated intolerance to standard therapy - which includes platinum&#xD;
             or fluoropyrimidine or taxane based chemotherapy.&#xD;
&#xD;
          2. Patients must have measurable disease.&#xD;
&#xD;
          3. Age ≥ 21 years&#xD;
&#xD;
          4. ECOG performance status (PS) of 0 to 1&#xD;
&#xD;
          5. Life expectancy at least 3 months&#xD;
&#xD;
          6. Patients must have normal organ and marrow function as defined below:&#xD;
&#xD;
               -  Absolute neutrophil count (ANC) ≥ 1,500/mcL&#xD;
&#xD;
               -  Platelets ≥ 100,000/mcL&#xD;
&#xD;
               -  Total bilirubin within normal institutional limits&#xD;
&#xD;
               -  AST(SGOT)/ALT(SGPT) ≤ 2.5 X institutional upper limit of normal&#xD;
&#xD;
               -  Creatinine &lt;1.5x normal institutional limits&#xD;
&#xD;
          7. Patients must be HLA-A*24:02&#xD;
&#xD;
          8. Patients must have recovered (&lt; grade 1) from all reversible treatment toxicity from&#xD;
             prior chemotherapy, radiotherapy or surgery.&#xD;
&#xD;
          9. Ability to understand and the willingness to sign a written informed consent document.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Patients receiving any other investigational products&#xD;
&#xD;
          2. Patients who have previously received prior nivolumab or PD-/L1 blockade therapy&#xD;
&#xD;
          3. Active autoimmune disease requiring disease-modifying therapy.&#xD;
&#xD;
          4. Concurrent systemic steroid therapy higher than physiologic dose (equivalent of&#xD;
             prednisolone 10mg daily)&#xD;
&#xD;
          5. Any form of active primary or secondary immunodeficiency.&#xD;
&#xD;
          6. History of significant gastrointestinal bleeding that required intervention within the&#xD;
             prior 1 month is ineligible; inherited bleeding diathesis or coagulopathy.&#xD;
&#xD;
          7. Serious non healing wound and peptic ulcer disease&#xD;
&#xD;
          8. Previous history of intestinal perforation&#xD;
&#xD;
          9. Symptomatic central nervous system (CNS) metastasis&#xD;
&#xD;
         10. Uncontrolled intercurrent illness including, but not limited to, ongoing or active&#xD;
             infection, uncontrolled hypertension (systolic &gt;160 mmHg and/or diastolic &gt;100 mmHg),&#xD;
             symptomatic congestive heart failure, unstable angina pectoris, myocardial&#xD;
             infarction/cerebrovascular event (≤ 6 months prior to study entry), cardiac&#xD;
             arrhythmia, or psychiatric illness/social situations that would limit compliance with&#xD;
             study requirements, long term systemic immunosuppressant or corticosteroid, and active&#xD;
             viral hepatitis.&#xD;
&#xD;
         11. Women who are breast-feeding or pregnant are excluded from this study.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Wei Peng Yong</last_name>
    <role>Principal Investigator</role>
    <affiliation>National University Hospital, Singapore</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Wei Peng Yong</last_name>
    <phone>(65) 6779 5555</phone>
    <email>Wei_Peng_Yong@nuhs.edu.sg</email>
  </overall_contact>
  <location>
    <facility>
      <name>National University Hospital</name>
      <address>
        <city>Singapore</city>
        <zip>119074</zip>
        <country>Singapore</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Wei Peng Yong</last_name>
      <phone>(65) 6779 5555</phone>
      <email>Wei_Peng_Yong@nuhs.edu.sg</email>
    </contact>
  </location>
  <location_countries>
    <country>Singapore</country>
  </location_countries>
  <reference>
    <citation>Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006 Jun 20;24(18):2903-9. doi: 10.1200/JCO.2005.05.0245.</citation>
    <PMID>16782930</PMID>
  </reference>
  <reference>
    <citation>Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007 Dec 15;67(24):11601-11. doi: 10.1158/0008-5472.CAN-07-3243.</citation>
    <PMID>18089789</PMID>
  </reference>
  <reference>
    <citation>Janunger KG, Hafstrom L, Nygren P, Glimelius B; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in gastric cancer. Acta Oncol. 2001;40(2-3):309-26. doi: 10.1080/02841860151116385.</citation>
    <PMID>11441938</PMID>
  </reference>
  <verification_date>April 2019</verification_date>
  <study_first_submitted>December 20, 2018</study_first_submitted>
  <study_first_submitted_qc>December 20, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 21, 2018</study_first_posted>
  <last_update_submitted>April 5, 2019</last_update_submitted>
  <last_update_submitted_qc>April 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">April 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Nivolumab</keyword>
  <keyword>Ipilimumab</keyword>
  <keyword>OTSGC-A24</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stomach Neoplasms</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nivolumab</mesh_term>
    <mesh_term>Ipilimumab</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT03784040
org study id: GA01/03/18
secondary id: 2018/00422
nct id: NCT03784040
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
The primary hypothesis is that cancer vaccine can convert non-immunogenic gastric cancer into
      immunogenic phenotype susceptible to PD1 inhibition. This would lead to an improved
      radiological response rate and favorable immune contexture for immune checkpoint blockade
Primary Objectives

        1. Safety cohorts: To evaluate the safety of OTSGC-A24 and nivolumab (+ ipilimumab) in
           patients with refractory gastric cancer.

        2. Arm A: To determine the objective response rate of OTSGC-A24 and nivolumab in advanced
           gastric cancer.

        3. Arm B: To determine the objective response rate of OTSGC-A24 and nivolumab + ipilimumab
           in advanced gastric cancer.

      Secondary Objectives

        1. To compare the difference in objective response rates between Arm A and Arm B

        2. To compare the tumoral immune contexture and PDL-1 expression before treatment, after
           OTSGC-A24, and after nivolumab (+ ipilimumab) in combination with OTSGC-A24.

        3. To determine the serum cytotoxic T-cell response using enzyme-linked immunospot assay
           (ELISPOT) in PBMC.

        4. To determine the progression-free survival (PFS) and overall survival (OS) of Arm A and
           Arm B.

        5. To evaluate the effect of OTSGC-A24 and nivolumab + ipilimumab on clinical and immune PD
           markers.

        6. Evaluate the effects of treatment on peripheral T-cell phenotypic profiles with
           epitope-specificities by coupling mass cytometric analyses with highly-multiplexed
           peptide-MHC tetramer staining technology.

        7. Identify potential biomarkers for treatment response and mechanisms of secondary
           resistance by studying gene expression profiles and phenotypic/functional markers of
           tumour and infiltrating immune cells.

      End Points - Efficacy

      The endpoints for efficacy are:

        -  Induction of specific CTL response after vaccination

        -  Response rate

        -  Progression-free survival

        -  Overall survival End Points - Safety

      The endpoints for safety are:

      • overall adverse events observed, treatment-related adverse events, and category (eg
      percentage of patients with any-grade treatment-related adverse events and grade 3-4
      treatment-related adverse events).
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Event and Adverse Drug Reaction
time frame: 3 years
measure: Response Rate
time frame: 3 years
measure: Rate of induction of specific CTL response
time frame: 3 years
measure: Progression-free Survival
time frame: 3 years
measure: Overall Survival
time frame: 3 years
arm group label: (Arm A) OTSGC-A24 + nivolumab
arm group type: Experimental
description: Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14 each 28 day cycle (q28d) for up to 24 months.
arm group label: (Arm B) OTSGC-A24 + nivolumab + ipilimumab
arm group type: Experimental
description: Study subjects will receive nivolumab 240 mg intravenously (IV) and OTSGC-A24 consisted of 1 μmol (~1 mg) of OTSGC-A24-Fo, OTSGC-A24-De, OTSGC-A24-Ki, OTSGC-A24-VE1 and OTSGC-A24-Ur 1.0 μmol (as API) administered subcutaneously on Day 1 and D14. Ipilimumab 1mg/kg (IV) will be administered q6w (i.e. C1D1, C2D15, C3D1 …) of each 28 day cycle for up to 24 months.
intervention type: Drug
intervention name: OTSGC-A24
description: OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
arm group label: (Arm A) OTSGC-A24 + nivolumab
arm group label: (Arm B) OTSGC-A24 + nivolumab + ipilimumab
intervention type: Drug
intervention name: Nivolumab
description: OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
arm group label: (Arm A) OTSGC-A24 + nivolumab
arm group label: (Arm B) OTSGC-A24 + nivolumab + ipilimumab
intervention type: Drug
intervention name: Ipilimumab
description: OTSGC-A24 is administered as a subcutaneous (under the skin) injection. Nivolumab and ipilimumab are administered by intravenous (IV) infusion, meaning the drug is given through a catheter in a vein. A pump will be used to ensure the correct amount of medicine is given through the catheter. The nivolumab and ipilimumab infusions each take about 30 minutes. There will be a break of about 30 minutes in between the nivolumab and ipilimumab infusions (if given on the same day). OTSGC-A24 and nivolumab are administered every 2 weeks, while ipilimumab is administered every 6 weeks.
arm group label: (Arm B) OTSGC-A24 + nivolumab + ipilimumab
criteria: 
gender: All
minimum age: 21 Years
maximum age: 99 Years
healthy volunteers: No
last name: Wei Peng Yong
role: Principal Investigator
affiliation: National University Hospital, Singapore
last name: Wei Peng Yong
phone: (65) 6779 5555
email: Wei_Peng_Yong@nuhs.edu.sg
facility: 
status: Recruiting
contact: 
country: Singapore
citation: Wagner AD, Grothe W, Haerting J, Kleber G, Grothey A, Fleig WE. Chemotherapy in advanced gastric cancer: a systematic review and meta-analysis based on aggregate data. J Clin Oncol. 2006 Jun 20;24(18):2903-9. doi: 10.1200/JCO.2005.05.0245.
PMID: 16782930
citation: Ishikawa N, Takano A, Yasui W, Inai K, Nishimura H, Ito H, Miyagi Y, Nakayama H, Fujita M, Hosokawa M, Tsuchiya E, Kohno N, Nakamura Y, Daigo Y. Cancer-testis antigen lymphocyte antigen 6 complex locus K is a serologic biomarker and a therapeutic target for lung and esophageal carcinomas. Cancer Res. 2007 Dec 15;67(24):11601-11. doi: 10.1158/0008-5472.CAN-07-3243.
PMID: 18089789
citation: Janunger KG, Hafstrom L, Nygren P, Glimelius B; SBU-group. Swedish Council of Technology Assessment in Health Care. A systematic overview of chemotherapy effects in gastric cancer. Acta Oncol. 2001;40(2-3):309-26. doi: 10.1080/02841860151116385.
PMID: 11441938
responsible party type: Sponsor
mesh term: Stomach Neoplasms
mesh term: Nivolumab
mesh term: Ipilimumab
sharing ipd: No